Anthony Krantis - Academia.edu (original) (raw)
Papers by Anthony Krantis
Neurosci Lett, 1981
Localization of [3H]GABA in the guinea-pig myenteric plexus has been studied using light microsco... more Localization of [3H]GABA in the guinea-pig myenteric plexus has been studied using light microscopic autoradiography. In the presence of beta-alanine, 10(-3) M, an inhibitor of glial cell high affinity GABA transport, [3H]GABA was transported by a high affinity uptake system into neuronal elements of the plexus. Scattered neurones accumulating [3H]GABA showed localization of silver grains over the soma and axonal processes. In addition a large population of uptake sites for [3H]GABA was found within the secondary and tertiary meshworks of the plexus so that dense accumulations of silver grains were observed localized over distinct 'tracts' within all three meshworks of the plexus. These results are considered to provide strong evidence for GABAergic neurons in the enteric nervous system.
![Research paper thumbnail of Selective uptake of γ-[3H]aminobutyric acid by neural elements and vascular nerves of the rat intestinal submucosa](https://attachments.academia-assets.com/71763311/thumbnails/1.jpg)
](Neuroscience Letters, 1990
Laminae of the rat intestinal submucosa were examined autoradiographically for ?,-[3H]aminobutyri... more Laminae of the rat intestinal submucosa were examined autoradiographically for ?,-[3H]aminobutyric acid ([3H]GABA) high-affinity uptake sites. In the presence of 10 3 M fl-alanine, to prevent high-affinity uptake and localization of radiolabelled GABA by glia. [3H]GABA was accumulated into elements of Henle's or Schabadascb's plexus, and vascular nerves. Densely labelled fibres in the nerve plexus could be followed through the ganglia and interconnecting fasciculi, and often formed a dense neuropil in the ganglia. Cell soma were never labelled. Densely labelled fibres of the nerve plexus were sometimes found to be contiguous with fibres coursing with the blood vessels. All labelling could be prevented by the neural specific high-affinity uptake blocker, L-diaminobutyric acid (L-DABA; 10-~ M). ~-Aminobutyric acid (GABA) is a transmitter of myenteric interneurons in the guinea pig (for reviews see refs. 21, 4) and there is increasing evidence for GABA to have a similar function in the rat, cat and human [11, 16, 17, 21, 23]. GABAergic neurones identified autoradiographically in the rat small intestine [18, 23], are present within the myenteric plexus and its innervation of the circular muscle layer. This corresponds to the established actions of applied GABA in the rat intestine, where GABA and its agonists either stimulate or inhibit intrinsic motor neurones via distinct neural receptors, the bicuculline sensitive GABAA and baclofen sensitive GABAB sites [11, 16]. In addition, blockade of these receptors reduces motility [16] indicative of some modulatory role for the enteric GABAergic system in control of intestinal motility similar to its proposed function in the guinea pig intestine [12, 221. Recently, Harty and Franklin [6, 7] reported that GABA simultaneously stimulated gastrin and inhibited somatostatin release from isolated segments of the rat gastric antrum.
Curr Opin Pharmacol, 2001
The American journal of physiology, 1998
Spontaneous relaxations occurring within motor activity in the rat gastroduodenum in vivo can be ... more Spontaneous relaxations occurring within motor activity in the rat gastroduodenum in vivo can be distinguished by their dependence on either nitric oxide (NO) or ATP. We examined the interaction of gamma-aminobutyric acid (GABA) and vasoactive intestinal peptide (VIP) within pathways controlling this activity in the antrum (S) and duodenum (D) of anesthetized Sprague-Dawley rats, using miniaturized extraluminal foil strain gauges oriented perpendicular to (S1, D1) or in the axis of (S2) the circular smooth muscle. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg iv) attenuated (P < 0.05) antral relaxations and, in the duodenum, nonpropagating "intergroup" relaxations. The GABAA receptor antagonist bicuculline (350 micrograms/kg sc) had similar effects. The GABAA agonist 3-amino-1-propanesulfonic acid stimulated L-NAME-sensitive relaxations at S1 and D1. Propagating "grouped" responses were unchanged. VIP (6 micrograms/kg iv) always ...
Neuroscience Letters, 1986
![Research paper thumbnail of Selective uptake of γ-[3H]aminobutyric acid by neural elements and vascular nerves of the rat intestinal submucosa](https://attachments.academia-assets.com/71763300/thumbnails/1.jpg)
](Neuroscience Letters, 1990
Laminae of the rat intestinal submucosa were examined autoradiographically for ?,-[3H]aminobutyri... more Laminae of the rat intestinal submucosa were examined autoradiographically for ?,-[3H]aminobutyric acid ([3H]GABA) high-affinity uptake sites. In the presence of 10 3 M fl-alanine, to prevent high-affinity uptake and localization of radiolabelled GABA by glia. [3H]GABA was accumulated into elements of Henle's or Schabadascb's plexus, and vascular nerves. Densely labelled fibres in the nerve plexus could be followed through the ganglia and interconnecting fasciculi, and often formed a dense neuropil in the ganglia. Cell soma were never labelled. Densely labelled fibres of the nerve plexus were sometimes found to be contiguous with fibres coursing with the blood vessels. All labelling could be prevented by the neural specific high-affinity uptake blocker, L-diaminobutyric acid (L-DABA; 10-~ M). ~-Aminobutyric acid (GABA) is a transmitter of myenteric interneurons in the guinea pig (for reviews see refs. 21, 4) and there is increasing evidence for GABA to have a similar function in the rat, cat and human [11, 16, 17, 21, 23]. GABAergic neurones identified autoradiographically in the rat small intestine [18, 23], are present within the myenteric plexus and its innervation of the circular muscle layer. This corresponds to the established actions of applied GABA in the rat intestine, where GABA and its agonists either stimulate or inhibit intrinsic motor neurones via distinct neural receptors, the bicuculline sensitive GABAA and baclofen sensitive GABAB sites [11, 16]. In addition, blockade of these receptors reduces motility [16] indicative of some modulatory role for the enteric GABAergic system in control of intestinal motility similar to its proposed function in the guinea pig intestine [12, 221. Recently, Harty and Franklin [6, 7] reported that GABA simultaneously stimulated gastrin and inhibited somatostatin release from isolated segments of the rat gastric antrum.
Gastroenterology, 1997
This is unlikely, however, because we have shown histologically that Clinical Service our strippe... more This is unlikely, however, because we have shown histologically that Clinical Service our stripped guinea pig ileum preparations are entirely devoid of EDUARDO MAURIÑ O associated muscularis externa and, therefore, myenteric plexus. 3 It is Small Bowel Section more likely that the differences observed between the two studies Clinical Service reflect the inherent differences in enteric control of electrolyte trans-Hospital de Gastroenterologia port in the guinea pig and rat. Significant differences between these Buenos Aires, Argentina two species have been shown with respect to the GABAergic innervation of the gut wall. 4,5
News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society, 2000
gamma-Aminobutyric acid (GABA) is a transmitter of enteric interneurons, targeting excitatory GAB... more gamma-Aminobutyric acid (GABA) is a transmitter of enteric interneurons, targeting excitatory GABA(A) or inhibitory GABA(B) receptors that modulate motility and mucosal function. Enteric GABA may also subserve hormonal and paracrine signaling. Disruption in gastrointestinal function following perturbation of enteric GABA receptors presents potential new target sites for drug development.
Gastroenterology, 1995
In celiac sprue cholecystokinin (CCK) release is impaired, which contributes to malabsorption. Wh... more In celiac sprue cholecystokinin (CCK) release is impaired, which contributes to malabsorption. Whether this defect results from CCK cell dysfunction or from a reduced intraluminal stimulus due to a lack of nutrient's hydrolysis in the jejunum remains controversial. In the latter hypothesis, administration of a predigested diet would correct the defect. Our aim was thus to study the effect of protein pre-digestion on CCK release. Methods. On two separate days, 12 patients with celiac disease, 9 women and 3 men, mean age 39, range 30-45, were given a standard (Sondalis R , Clintec) and a semi-elemental (Reabilan", Clintec) liquid diet, The patients were divided in two groups: one with a flat jejunal mucosa (destructive type) (n=6) and one with normal architecture but infiltration of intra-epithelial lymphocytes (infiltrative type) (n=6). A control group (n=9) was also given the two liquid meals. CCK plasma levels were determined at 15 min intervals for 120 min by RIA and expressed as integrated release (IR). Results. Celiac patients had lower basal CCK values than controls: 0.64 _+ 0.1 vs 1.06 _+ 0.2 pmole/I, p<0.05. Both groups had diminished CCK responses compared to the control group (IR 55.6 _+ 11.4, 74.5 _+ 18 and 202 _ 24.9 pmole/I/120 min, respectively, p<0.05). No significant effect of pre-digestion of protein was observed in controls or in celiac patients (IR 62.4 +_ 20.9, 69.8 + 14.7 and 230.9 +-34.5 pmole/I/120 rain). Conclusion. Protein pre-digestion does not correct impairement of CCK post-prandial release in celiac patients. Moreover, in celiac patients on gluten-free diet impairement of CCK release persists in spite of improvement in mucosal atrophy. We have previously reported that, unlike isolated circular smooth muscle cells from the feline adult gastric antrum, feline newborn antral cells are unable to contract in response to myogenic agonists in the absence of extracellularcalcinm or to exogenous 1,4,5-inositol trisphosphate (IP3) after permeabilization. IP3 binding was determined in gastric antral circular smooth muscle tissue homogenates from adult cats and 10 day old kittens by the evaluating the competitive binding of D-myo-[3H] inositol 1,4,5-trisphosphate and cold 1,4,5-IP3 (0-200 pmoles). Receptor density (Bmax) and binding affinity (Kd) were determined by Scatchard analysis. Bmax was standardized to tissue protein content and expressed as fmol/mg. The binding affinity (Kd) was similar in both age groups at (30.5 nM + 3.5) in the adult and (32.5 nM + 7.6) in the kitten. However the receptor density (Bmax) was markedly decreased in the kitten at (760 fmol/mg + 162.0) compared to the adult (1755 fmol/mg + 251.6). The contractile response to the myogenic agonist cholecystokinin octapeptide (CCK-OP) which is transient in adult cells and sustained in kitten antral cells was used to further examine the functional role of IP3 and it's receptor. We have measured changes in the intracellular levels of 1, 2 diacylglycerol (DAG), an endogenous activator of protein kinase C, and IP3, which is known to release intracellular calcium stores. In adult antral tissue CCK-OP causes an early transient increase in the production of both DAG and IP3 while in the newborn antrum CCK-OP causes an early increase in IP3 and a sustained increase in DAG production. U73122, a phospholipase C inhibitor which blocks IP3 production, blocks the initial cona'action in adult antral cells but not the sustained contraction seen in kitten antral cells. We conclude that in feline antral circular smooth muscle ceils the 1,4,5-inositol trisphosphate receptor is characterized by a single binding site in both the kitten and adult cat. The binding affinity (Kd) was similar between the kitten and adult eat, however the receptor density (Bmax) in the kitten is approximately one-half that of the adult cat. The relative inaccessibility of IP3 sensitive intracellular calcium stores is associated with a shift in signal transduction pathways that are followed in response to myogenic agonists such as CCK-OP that results in sustained contraction and sustained production of DAG. We hypothesize that this relative inaccessibility of IP3 sensitive intracellular calcium may be due developmental immaturity of I]?3 receptors.
Journal of Pediatric Surgery, May 31, 2001
Background/Purpose: Nitric oxide (NO) mediates enteric smooth muscle relaxation and mucosal prote... more Background/Purpose: Nitric oxide (NO) mediates enteric smooth muscle relaxation and mucosal protection. The authors have identified an ontogenically determined pattern of enteric NO neural maturation that may render the distal gut of premature piglets susceptible to injury.
Peptides, Jun 30, 1992
The presence of a peptide capable of producing powerful contractions of rat small intestinal smoo... more The presence of a peptide capable of producing powerful contractions of rat small intestinal smooth muscle was detected in chromatographic fractions derived from porcine gastric corpus extracts. The pharmacological characteristics of this entity suggested that it might be galanin and on its purification to homogeneity, amino acid composition and sequence analysis demonstrated the identify of the gastric and intestinal forms of galanin. The presence of galanin in the gastric corpus tissue and its ability to affect gastric smooth muscle activity, gastrin release, and gastric acid secretion suggest potential important physiological roles for galanin in the stomach.
Gastroenterology, 1995
Oral administration of DSS has been reported to induce an acute and chronic colitis in mice. Earl... more Oral administration of DSS has been reported to induce an acute and chronic colitis in mice. Earlier, we showed that lymphocytes" were more prominent during the chronic rather than the acute phase of this model Active Crohn's disease and some chronic expei'imental colitis models are characterized by a Thl cytokine profile. The aim 0four study was to evaluate if the chronic phase of DSS-induced colitis was characterized by a dysregulation of Thl/Th2 balance and how this would relate to mucosal regeneratio n. METHODS: Swiss Webster mice were fed 5% DSS in their drinking water for 7 days, followed by 2-5 weeks' consumption of water. Control mice received only wa~r. The mice given DSS were divided into 2 groups and sacrificed after 2 and 5 weeks resp. after stopping DSS administration. The different parts of their colons were isolated for histology and for immunohistochemistry on cryostat sections using specific monoclonal antibodies for T and B cells, macrophages, interferon-3, and interleukin-5 (IL-5). Colonic sections were scored for histological regeneration and inflammation. We also measured interferonw production by culture of colonic specimens, using specific bioassays such as t6e'murine WEHI 279 cell line. RESULTS: Two weeks after stopping DSS the colonic epithelium had only partially healed, showing various stages of regeneration, starting from the neighboring epithelium and bridging over focal crypt defects in a!! parts of the colon. In these areas the mucosa contained large lymphoid aggregates, which consisted mainly of B cells and some surrounding CD4 positive T cells. The basal parts of the lamina propria contained macrophages and CD4 T cells, which aiso showed a focal increase of interferon-3, staining, compared to control animals. However, IL-5 staining was virtually absent in both DSS and control colons, These results were confirmed by an increased production of interferon-3, production in the colon cultures of DSS-treated animals versus controls. These findings were still observed 5 weeks after stopping DSS in some mice, albeit less extensive. CONCLUSIONS: Chronic DSS-induced colitis is characterized by focal epithelial regeneration and a Thl cytokine profil e. We postulate that chronic immune activation mediated by Thl cells could explain the chronicity of this model:
Journal of the autonomic nervous system, Jan 3, 1995
In the enteric nervous system, gamma-aminobutyric acid (GABA) is a transmitter of interneurons wh... more In the enteric nervous system, gamma-aminobutyric acid (GABA) is a transmitter of interneurons which are proposed to innervate excitatory and inhibitory motor neurons. Nitric oxide (NO) is a putative transmitter of enteric inhibitory motor nerves targeted by GABA. In addition, NO is synthesized by a variety of enteric nerves throughout the gut wall indicative of its potential to be a transmitter of other nerve types, including interneurons. We sought to determine if some populations of nitrergic neurons are interneurons in human infant colon. As enteric neural GABA is exclusive to interneurons, colocalization with NO synthase-related NADPH diaphorase was examined. GABA-transaminase (GABA-T) immunohistochemistry was used to identify GABAergic neurons and a histochemical protocol was used as a marker of neuronal NO synthase-related NADPH diaphorase activity in enteric layers. GABA-T immunoreactive neurons were seen in the ganglionated nerve networks of the myenteric and submucosal lay...
Journal of the autonomic nervous system, Jan 11, 1997
Neuropeptide Y is a neurotransmitter in both the central nervous system and the enteric nervous s... more Neuropeptide Y is a neurotransmitter in both the central nervous system and the enteric nervous system. Neuropeptide Y receptors have been demonstrated by in situ hybridization and ligand binding techniques to be present in both of these systems. In this study we report on the distribution of the Y1 isoform of the neuropeptide Y receptor (YY1) in human colon using an antibody raised against the Y1 receptor. This method permits greater resolution in determining the distribution of the receptor and provides the opportunity to study neurotransmitter markers in relationship to the Y1 receptor. Y1 receptor immunoreactivity was localized within ganglionic neurons and axons of the myenteric and submucosal nerve networks, axons within the muscularis mucosae, longitudinal and circular smooth muscle layers, sympathetic nerve fibers around blood vessels and within scattered cells in the mucosa and basal cells of the crypts. Neuropeptide Y/Y1 double staining showed that the peptide and its Y1 r...
Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Société canadienne des sciences pharmaceutiques
Traditional Chinese medicines (TCM) are believed by many to be safe and used for self-medication ... more Traditional Chinese medicines (TCM) are believed by many to be safe and used for self-medication without supervision. Although the risk appears to be low, certain TCM have been associated with a number of serious adverse reactions. A preliminary study was undertaken with 12 products using a human cytochrome P450 (CYP450) isozyme assay to determine if these products could affect human drug metabolism. Aliquots of samples were analyzed directly or as extracts for their potential to affect CYP450 2C9, 2C19, 2D6, and 3A4 mediated-metabolism of marker substrates using an in vitro fluorometric microtiter plate assay. One product was found to be a Chinese Proprietary Medicine (CPM). Most aqueous extracts inhibited CYP450 mediated-metabolism of at least 3 isozymes (ranging from 25-100%). All liquid samples markedly inhibited the metabolism of all 4 isozymes. De le ke chuan kang and Rensheng dao were the strongest CYP450 inhibitors. Our in vitro findings demonstrate that TCM can inhibit CYP4...
Journal of the Autonomic Nervous System, 1998
GABA, somatostatin and enkephalin are neurotransmitters of enteric interneurons and comprise part... more GABA, somatostatin and enkephalin are neurotransmitters of enteric interneurons and comprise part of the intrinsic neural circuits regulating peristalsis. Within the relaxation phase of reflex peristalsis, nitric oxide (NO) is released by inhibitory motor neurons and perhaps enteric interneurons as well. Previously, we identified by GABA transaminase (GABA-T) immunohistochemistry, a subpopulation of GABAergic interneurons in the human colon which also contain NO synthase activity and hence produce NO. In this study, we have examined further the capacity for cotransmission within the GABAergic innervation in human colon. The expression of two important neuropeptides within GABAergic neurons was determined by combined double-labelled immunocytochemistry using antibodies for GABA-T, enkephalin and somatostatin, together with the demonstration of NO synthase-related NADPH diaphorase staining in cryosectioned colon. Both neuropeptides were found in GABAergic neurons of the colon. The evidence presented herein confirms the colocalization of NO synthase activity and GABA-T immunoreactivity in subpopulations of enteric neurons and further allows the neurochemical classification of GABAergic neurons of the human colon into three subsets: (i) neurons colocalizing somatostatin-like immunoreactivity representing about 40% of the GABAergic neurons, (ii) neurons colocalizing enkephalin-like immunoreactivity, about 9% of the GABAergic neurons and (iii) neurons colocalizing NO synthase activity, about 23% of the GABAergic neurons. This division of GABAergic interneurons into distinct subpopulations of neuropeptide or NO synthase containing cells is consistent with and provides an anatomical correlate for the pharmacology of these transmitters and the pattern of transmitter release during reflex peristalsis.
Neurosci Lett, 1981
Localization of [3H]GABA in the guinea-pig myenteric plexus has been studied using light microsco... more Localization of [3H]GABA in the guinea-pig myenteric plexus has been studied using light microscopic autoradiography. In the presence of beta-alanine, 10(-3) M, an inhibitor of glial cell high affinity GABA transport, [3H]GABA was transported by a high affinity uptake system into neuronal elements of the plexus. Scattered neurones accumulating [3H]GABA showed localization of silver grains over the soma and axonal processes. In addition a large population of uptake sites for [3H]GABA was found within the secondary and tertiary meshworks of the plexus so that dense accumulations of silver grains were observed localized over distinct 'tracts' within all three meshworks of the plexus. These results are considered to provide strong evidence for GABAergic neurons in the enteric nervous system.
Neuroscience Letters, 1990
Laminae of the rat intestinal submucosa were examined autoradiographically for ?,-[3H]aminobutyri... more Laminae of the rat intestinal submucosa were examined autoradiographically for ?,-[3H]aminobutyric acid ([3H]GABA) high-affinity uptake sites. In the presence of 10 3 M fl-alanine, to prevent high-affinity uptake and localization of radiolabelled GABA by glia. [3H]GABA was accumulated into elements of Henle's or Schabadascb's plexus, and vascular nerves. Densely labelled fibres in the nerve plexus could be followed through the ganglia and interconnecting fasciculi, and often formed a dense neuropil in the ganglia. Cell soma were never labelled. Densely labelled fibres of the nerve plexus were sometimes found to be contiguous with fibres coursing with the blood vessels. All labelling could be prevented by the neural specific high-affinity uptake blocker, L-diaminobutyric acid (L-DABA; 10-~ M). ~-Aminobutyric acid (GABA) is a transmitter of myenteric interneurons in the guinea pig (for reviews see refs. 21, 4) and there is increasing evidence for GABA to have a similar function in the rat, cat and human [11, 16, 17, 21, 23]. GABAergic neurones identified autoradiographically in the rat small intestine [18, 23], are present within the myenteric plexus and its innervation of the circular muscle layer. This corresponds to the established actions of applied GABA in the rat intestine, where GABA and its agonists either stimulate or inhibit intrinsic motor neurones via distinct neural receptors, the bicuculline sensitive GABAA and baclofen sensitive GABAB sites [11, 16]. In addition, blockade of these receptors reduces motility [16] indicative of some modulatory role for the enteric GABAergic system in control of intestinal motility similar to its proposed function in the guinea pig intestine [12, 221. Recently, Harty and Franklin [6, 7] reported that GABA simultaneously stimulated gastrin and inhibited somatostatin release from isolated segments of the rat gastric antrum.
Curr Opin Pharmacol, 2001
The American journal of physiology, 1998
Spontaneous relaxations occurring within motor activity in the rat gastroduodenum in vivo can be ... more Spontaneous relaxations occurring within motor activity in the rat gastroduodenum in vivo can be distinguished by their dependence on either nitric oxide (NO) or ATP. We examined the interaction of gamma-aminobutyric acid (GABA) and vasoactive intestinal peptide (VIP) within pathways controlling this activity in the antrum (S) and duodenum (D) of anesthetized Sprague-Dawley rats, using miniaturized extraluminal foil strain gauges oriented perpendicular to (S1, D1) or in the axis of (S2) the circular smooth muscle. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg iv) attenuated (P < 0.05) antral relaxations and, in the duodenum, nonpropagating "intergroup" relaxations. The GABAA receptor antagonist bicuculline (350 micrograms/kg sc) had similar effects. The GABAA agonist 3-amino-1-propanesulfonic acid stimulated L-NAME-sensitive relaxations at S1 and D1. Propagating "grouped" responses were unchanged. VIP (6 micrograms/kg iv) always ...
Neuroscience Letters, 1986
Neuroscience Letters, 1990
Laminae of the rat intestinal submucosa were examined autoradiographically for ?,-[3H]aminobutyri... more Laminae of the rat intestinal submucosa were examined autoradiographically for ?,-[3H]aminobutyric acid ([3H]GABA) high-affinity uptake sites. In the presence of 10 3 M fl-alanine, to prevent high-affinity uptake and localization of radiolabelled GABA by glia. [3H]GABA was accumulated into elements of Henle's or Schabadascb's plexus, and vascular nerves. Densely labelled fibres in the nerve plexus could be followed through the ganglia and interconnecting fasciculi, and often formed a dense neuropil in the ganglia. Cell soma were never labelled. Densely labelled fibres of the nerve plexus were sometimes found to be contiguous with fibres coursing with the blood vessels. All labelling could be prevented by the neural specific high-affinity uptake blocker, L-diaminobutyric acid (L-DABA; 10-~ M). ~-Aminobutyric acid (GABA) is a transmitter of myenteric interneurons in the guinea pig (for reviews see refs. 21, 4) and there is increasing evidence for GABA to have a similar function in the rat, cat and human [11, 16, 17, 21, 23]. GABAergic neurones identified autoradiographically in the rat small intestine [18, 23], are present within the myenteric plexus and its innervation of the circular muscle layer. This corresponds to the established actions of applied GABA in the rat intestine, where GABA and its agonists either stimulate or inhibit intrinsic motor neurones via distinct neural receptors, the bicuculline sensitive GABAA and baclofen sensitive GABAB sites [11, 16]. In addition, blockade of these receptors reduces motility [16] indicative of some modulatory role for the enteric GABAergic system in control of intestinal motility similar to its proposed function in the guinea pig intestine [12, 221. Recently, Harty and Franklin [6, 7] reported that GABA simultaneously stimulated gastrin and inhibited somatostatin release from isolated segments of the rat gastric antrum.
Gastroenterology, 1997
This is unlikely, however, because we have shown histologically that Clinical Service our strippe... more This is unlikely, however, because we have shown histologically that Clinical Service our stripped guinea pig ileum preparations are entirely devoid of EDUARDO MAURIÑ O associated muscularis externa and, therefore, myenteric plexus. 3 It is Small Bowel Section more likely that the differences observed between the two studies Clinical Service reflect the inherent differences in enteric control of electrolyte trans-Hospital de Gastroenterologia port in the guinea pig and rat. Significant differences between these Buenos Aires, Argentina two species have been shown with respect to the GABAergic innervation of the gut wall. 4,5
News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society, 2000
gamma-Aminobutyric acid (GABA) is a transmitter of enteric interneurons, targeting excitatory GAB... more gamma-Aminobutyric acid (GABA) is a transmitter of enteric interneurons, targeting excitatory GABA(A) or inhibitory GABA(B) receptors that modulate motility and mucosal function. Enteric GABA may also subserve hormonal and paracrine signaling. Disruption in gastrointestinal function following perturbation of enteric GABA receptors presents potential new target sites for drug development.
Gastroenterology, 1995
In celiac sprue cholecystokinin (CCK) release is impaired, which contributes to malabsorption. Wh... more In celiac sprue cholecystokinin (CCK) release is impaired, which contributes to malabsorption. Whether this defect results from CCK cell dysfunction or from a reduced intraluminal stimulus due to a lack of nutrient's hydrolysis in the jejunum remains controversial. In the latter hypothesis, administration of a predigested diet would correct the defect. Our aim was thus to study the effect of protein pre-digestion on CCK release. Methods. On two separate days, 12 patients with celiac disease, 9 women and 3 men, mean age 39, range 30-45, were given a standard (Sondalis R , Clintec) and a semi-elemental (Reabilan", Clintec) liquid diet, The patients were divided in two groups: one with a flat jejunal mucosa (destructive type) (n=6) and one with normal architecture but infiltration of intra-epithelial lymphocytes (infiltrative type) (n=6). A control group (n=9) was also given the two liquid meals. CCK plasma levels were determined at 15 min intervals for 120 min by RIA and expressed as integrated release (IR). Results. Celiac patients had lower basal CCK values than controls: 0.64 _+ 0.1 vs 1.06 _+ 0.2 pmole/I, p<0.05. Both groups had diminished CCK responses compared to the control group (IR 55.6 _+ 11.4, 74.5 _+ 18 and 202 _ 24.9 pmole/I/120 min, respectively, p<0.05). No significant effect of pre-digestion of protein was observed in controls or in celiac patients (IR 62.4 +_ 20.9, 69.8 + 14.7 and 230.9 +-34.5 pmole/I/120 rain). Conclusion. Protein pre-digestion does not correct impairement of CCK post-prandial release in celiac patients. Moreover, in celiac patients on gluten-free diet impairement of CCK release persists in spite of improvement in mucosal atrophy. We have previously reported that, unlike isolated circular smooth muscle cells from the feline adult gastric antrum, feline newborn antral cells are unable to contract in response to myogenic agonists in the absence of extracellularcalcinm or to exogenous 1,4,5-inositol trisphosphate (IP3) after permeabilization. IP3 binding was determined in gastric antral circular smooth muscle tissue homogenates from adult cats and 10 day old kittens by the evaluating the competitive binding of D-myo-[3H] inositol 1,4,5-trisphosphate and cold 1,4,5-IP3 (0-200 pmoles). Receptor density (Bmax) and binding affinity (Kd) were determined by Scatchard analysis. Bmax was standardized to tissue protein content and expressed as fmol/mg. The binding affinity (Kd) was similar in both age groups at (30.5 nM + 3.5) in the adult and (32.5 nM + 7.6) in the kitten. However the receptor density (Bmax) was markedly decreased in the kitten at (760 fmol/mg + 162.0) compared to the adult (1755 fmol/mg + 251.6). The contractile response to the myogenic agonist cholecystokinin octapeptide (CCK-OP) which is transient in adult cells and sustained in kitten antral cells was used to further examine the functional role of IP3 and it's receptor. We have measured changes in the intracellular levels of 1, 2 diacylglycerol (DAG), an endogenous activator of protein kinase C, and IP3, which is known to release intracellular calcium stores. In adult antral tissue CCK-OP causes an early transient increase in the production of both DAG and IP3 while in the newborn antrum CCK-OP causes an early increase in IP3 and a sustained increase in DAG production. U73122, a phospholipase C inhibitor which blocks IP3 production, blocks the initial cona'action in adult antral cells but not the sustained contraction seen in kitten antral cells. We conclude that in feline antral circular smooth muscle ceils the 1,4,5-inositol trisphosphate receptor is characterized by a single binding site in both the kitten and adult cat. The binding affinity (Kd) was similar between the kitten and adult eat, however the receptor density (Bmax) in the kitten is approximately one-half that of the adult cat. The relative inaccessibility of IP3 sensitive intracellular calcium stores is associated with a shift in signal transduction pathways that are followed in response to myogenic agonists such as CCK-OP that results in sustained contraction and sustained production of DAG. We hypothesize that this relative inaccessibility of IP3 sensitive intracellular calcium may be due developmental immaturity of I]?3 receptors.
Journal of Pediatric Surgery, May 31, 2001
Background/Purpose: Nitric oxide (NO) mediates enteric smooth muscle relaxation and mucosal prote... more Background/Purpose: Nitric oxide (NO) mediates enteric smooth muscle relaxation and mucosal protection. The authors have identified an ontogenically determined pattern of enteric NO neural maturation that may render the distal gut of premature piglets susceptible to injury.
Peptides, Jun 30, 1992
The presence of a peptide capable of producing powerful contractions of rat small intestinal smoo... more The presence of a peptide capable of producing powerful contractions of rat small intestinal smooth muscle was detected in chromatographic fractions derived from porcine gastric corpus extracts. The pharmacological characteristics of this entity suggested that it might be galanin and on its purification to homogeneity, amino acid composition and sequence analysis demonstrated the identify of the gastric and intestinal forms of galanin. The presence of galanin in the gastric corpus tissue and its ability to affect gastric smooth muscle activity, gastrin release, and gastric acid secretion suggest potential important physiological roles for galanin in the stomach.
Gastroenterology, 1995
Oral administration of DSS has been reported to induce an acute and chronic colitis in mice. Earl... more Oral administration of DSS has been reported to induce an acute and chronic colitis in mice. Earlier, we showed that lymphocytes" were more prominent during the chronic rather than the acute phase of this model Active Crohn's disease and some chronic expei'imental colitis models are characterized by a Thl cytokine profile. The aim 0four study was to evaluate if the chronic phase of DSS-induced colitis was characterized by a dysregulation of Thl/Th2 balance and how this would relate to mucosal regeneratio n. METHODS: Swiss Webster mice were fed 5% DSS in their drinking water for 7 days, followed by 2-5 weeks' consumption of water. Control mice received only wa~r. The mice given DSS were divided into 2 groups and sacrificed after 2 and 5 weeks resp. after stopping DSS administration. The different parts of their colons were isolated for histology and for immunohistochemistry on cryostat sections using specific monoclonal antibodies for T and B cells, macrophages, interferon-3, and interleukin-5 (IL-5). Colonic sections were scored for histological regeneration and inflammation. We also measured interferonw production by culture of colonic specimens, using specific bioassays such as t6e'murine WEHI 279 cell line. RESULTS: Two weeks after stopping DSS the colonic epithelium had only partially healed, showing various stages of regeneration, starting from the neighboring epithelium and bridging over focal crypt defects in a!! parts of the colon. In these areas the mucosa contained large lymphoid aggregates, which consisted mainly of B cells and some surrounding CD4 positive T cells. The basal parts of the lamina propria contained macrophages and CD4 T cells, which aiso showed a focal increase of interferon-3, staining, compared to control animals. However, IL-5 staining was virtually absent in both DSS and control colons, These results were confirmed by an increased production of interferon-3, production in the colon cultures of DSS-treated animals versus controls. These findings were still observed 5 weeks after stopping DSS in some mice, albeit less extensive. CONCLUSIONS: Chronic DSS-induced colitis is characterized by focal epithelial regeneration and a Thl cytokine profil e. We postulate that chronic immune activation mediated by Thl cells could explain the chronicity of this model:
Journal of the autonomic nervous system, Jan 3, 1995
In the enteric nervous system, gamma-aminobutyric acid (GABA) is a transmitter of interneurons wh... more In the enteric nervous system, gamma-aminobutyric acid (GABA) is a transmitter of interneurons which are proposed to innervate excitatory and inhibitory motor neurons. Nitric oxide (NO) is a putative transmitter of enteric inhibitory motor nerves targeted by GABA. In addition, NO is synthesized by a variety of enteric nerves throughout the gut wall indicative of its potential to be a transmitter of other nerve types, including interneurons. We sought to determine if some populations of nitrergic neurons are interneurons in human infant colon. As enteric neural GABA is exclusive to interneurons, colocalization with NO synthase-related NADPH diaphorase was examined. GABA-transaminase (GABA-T) immunohistochemistry was used to identify GABAergic neurons and a histochemical protocol was used as a marker of neuronal NO synthase-related NADPH diaphorase activity in enteric layers. GABA-T immunoreactive neurons were seen in the ganglionated nerve networks of the myenteric and submucosal lay...
Journal of the autonomic nervous system, Jan 11, 1997
Neuropeptide Y is a neurotransmitter in both the central nervous system and the enteric nervous s... more Neuropeptide Y is a neurotransmitter in both the central nervous system and the enteric nervous system. Neuropeptide Y receptors have been demonstrated by in situ hybridization and ligand binding techniques to be present in both of these systems. In this study we report on the distribution of the Y1 isoform of the neuropeptide Y receptor (YY1) in human colon using an antibody raised against the Y1 receptor. This method permits greater resolution in determining the distribution of the receptor and provides the opportunity to study neurotransmitter markers in relationship to the Y1 receptor. Y1 receptor immunoreactivity was localized within ganglionic neurons and axons of the myenteric and submucosal nerve networks, axons within the muscularis mucosae, longitudinal and circular smooth muscle layers, sympathetic nerve fibers around blood vessels and within scattered cells in the mucosa and basal cells of the crypts. Neuropeptide Y/Y1 double staining showed that the peptide and its Y1 r...
Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Société canadienne des sciences pharmaceutiques
Traditional Chinese medicines (TCM) are believed by many to be safe and used for self-medication ... more Traditional Chinese medicines (TCM) are believed by many to be safe and used for self-medication without supervision. Although the risk appears to be low, certain TCM have been associated with a number of serious adverse reactions. A preliminary study was undertaken with 12 products using a human cytochrome P450 (CYP450) isozyme assay to determine if these products could affect human drug metabolism. Aliquots of samples were analyzed directly or as extracts for their potential to affect CYP450 2C9, 2C19, 2D6, and 3A4 mediated-metabolism of marker substrates using an in vitro fluorometric microtiter plate assay. One product was found to be a Chinese Proprietary Medicine (CPM). Most aqueous extracts inhibited CYP450 mediated-metabolism of at least 3 isozymes (ranging from 25-100%). All liquid samples markedly inhibited the metabolism of all 4 isozymes. De le ke chuan kang and Rensheng dao were the strongest CYP450 inhibitors. Our in vitro findings demonstrate that TCM can inhibit CYP4...
Journal of the Autonomic Nervous System, 1998
GABA, somatostatin and enkephalin are neurotransmitters of enteric interneurons and comprise part... more GABA, somatostatin and enkephalin are neurotransmitters of enteric interneurons and comprise part of the intrinsic neural circuits regulating peristalsis. Within the relaxation phase of reflex peristalsis, nitric oxide (NO) is released by inhibitory motor neurons and perhaps enteric interneurons as well. Previously, we identified by GABA transaminase (GABA-T) immunohistochemistry, a subpopulation of GABAergic interneurons in the human colon which also contain NO synthase activity and hence produce NO. In this study, we have examined further the capacity for cotransmission within the GABAergic innervation in human colon. The expression of two important neuropeptides within GABAergic neurons was determined by combined double-labelled immunocytochemistry using antibodies for GABA-T, enkephalin and somatostatin, together with the demonstration of NO synthase-related NADPH diaphorase staining in cryosectioned colon. Both neuropeptides were found in GABAergic neurons of the colon. The evidence presented herein confirms the colocalization of NO synthase activity and GABA-T immunoreactivity in subpopulations of enteric neurons and further allows the neurochemical classification of GABAergic neurons of the human colon into three subsets: (i) neurons colocalizing somatostatin-like immunoreactivity representing about 40% of the GABAergic neurons, (ii) neurons colocalizing enkephalin-like immunoreactivity, about 9% of the GABAergic neurons and (iii) neurons colocalizing NO synthase activity, about 23% of the GABAergic neurons. This division of GABAergic interneurons into distinct subpopulations of neuropeptide or NO synthase containing cells is consistent with and provides an anatomical correlate for the pharmacology of these transmitters and the pattern of transmitter release during reflex peristalsis.