Chemical sympathectomy attenuates myenteric but not dorsal vagal complex Fos-like immunoreactivity induced by cholecystokinin-8 in the rat (original) (raw)
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Neuroscience Letters, 2005
The objective of this study was to measure the relative efficacy and potency of cholecystokinin-8 (CCK-8) given by intraperitoneal (i.p.) and intravenous (i.v.) injection to stimulate Fos-like immunoreactivity (Fos-LI) in neurons of the myenteric plexus in the duodenum and jejunum. The subjects for his experiment were 40 male Sprague-Dawley rats divided into eight treatment groups (n = 5 rats per treatment). Four groups of rats were injected with 5, 10, and 40 g/kg sulfated CCK-8 and saline (control) i.p., and the remaining groups with the same treatments i.v. We then detected Fos-LI, a marker for neuronal activation, in the myenteric plexus of the duodenum and jejunum, in response to the previous doses and routes. All of the CCK-8 doses administered by both routes increased Fos-LI in the myenteric plexus of the duodenum and jejunum significantly more than saline did. Although both routes were efficacious in increasing Fos-LI, CCK-8 i.p. was significantly more potent than CCK-8 i.v. These data provide immunohistochemical evidence that i.p. administration of CCK-8 is a more potent stimulant of Fos-LI in the neurons of the myenteric plexus of the duodenum and jejunum than i.v. injection.
Regulatory Peptides, 2008
The enteric nervous system (ENS: myenteric and submucosal plexuses) of the gastrointestinal tract may have a role in the reduction of food intake by cholecystokinin (CCK). Exogenous cholecystokinin-8 (CCK-8) activates the myenteric plexus and the feeding control areas of the dorsal vagal complex (DVC) of the brainstem. An increasing number of reports, however, have shown that CCK-58 is the sole or the major circulating form of CCK in rat, human and dog, and that it is qualitatively different from CCK-8 in evoking various gastrointestinal physiological responses (e.g., contraction of the gallbladder and exocrine pancreatic secretion). In the current report, we compared the abilities of exogenous CCK-58 to activate the myenteric plexus and the dorsal vagal complex with those of exogenous CCK-8 by quantifying Fos-like immunoreactivity (Fos-LI; a marker for neuronal activation). We report that CCK-58 (1, 3, and 5 nmol/kg) increased Fos-LI in the myenteric plexus (p b 0.001) and in the DVC (p b 0.001) compared to the saline vehicle. The highest dose of CCK-58 increased Fos-LI more than an equimolar dose of CCK-8 in the myenteric plexus and the area postrema. Thus, CCK-8 and CCK-58 produce the same qualitative pattern of activation of central and peripheral neurons, but do not provoke identical quantitative patterns at higher doses. The different patterns produced by the two peptides at higher doses, in areas open to the circulation (myenteric plexus and area postrema) may reflect endocrine actions not observed at lower doses.
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2007
We hypothesized that endogenous CCK reduces food intake by activating the dorsal vagal complex (DVC) and the myenteric neurons of the gut. To test this hypothesis, adult rats were given camostat mesilate; a nonnutrient releaser of endogenous CCK, by orogastric gavage, and Fos-like immunoreactivity (Fos-LI) was quantified in the DVC and the myenteric plexus. The results for endogenous CCK were compared with those for exogenous CCK-8. Exogenous CCK-8 reduced food intake and stimulated Fos-LI in the DVC and in myenteric neurons of the duodenum and jejunum. In comparison, endogenous CCK reduced food intake and increased DVC Fos-LI but did not increase Fos-LI in the myenteric plexus. Similar to CCK-8, devazepide, a specific CCK 1 receptor antagonist, and not L365,260, a specific CCK2 receptor antagonist, attenuated the reduction of food intake by camostat. In addition, Fos-LI in the DVC in response to both exogenous CCK-8 and camostat administration was significantly attenuated by vagotomy, as well as by blocking CCK 1 receptors. These results demonstrate for the first time that reduction of food intake in adult rats by endogenous CCK released by a nonnutrient mechanism requires CCK 1 receptors, the vagus nerve, and activation of the DVC, but not the myenteric plexus.
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 2002
Cholecystokinin (CCK) is a potential mediator of gastrointestinal vasodilatation during digestion. To determine whether CCK influences sympathetic vasomotor function, we examined the effect of systemic CCK administration on mean arterial blood pressure (MAP), heart rate (HR), lumbar sympathetic nerve discharge (LSND), splanchnic sympathetic nerve discharge (SSND), and the discharge of presympathetic neurons of the rostral ventrolateral medulla (RVLM) in α-chloralose-anesthetized rats. CCK (1–8 μg/kg iv) reduced MAP, HR, and SSND and transiently increased LSND. Vagotomy abolished the effects of CCK on MAP and SSND as did the CCK-A receptor antagonist devazepide (0.5 mg/kg iv). The bradycardic effect of CCK was unaltered by vagotomy but abolished by devazepide. CCK increased superior mesenteric arterial conductance but did not alter iliac conductance. CCK inhibited a subpopulation (∼49%) of RVLM presympathetic neurons whereas ∼28% of neurons tested were activated by CCK. The effects o...
Brain Research, 2005
We utilized a diaminobenzidine reaction enhanced with nickel to compare dorsal vagal complex (DVC) and myenteric neuronal Fos-Like immunoreactivity (Fos-LI), in response to sulfated cholecystokinin-8 (CCK-8) (5, 10, 20, 40 Ag/kg), among Sprague -Dawley (SD), Standard Long -Evans (SLE), Otsuka Long-Evans Tokushima Fatty (OLETF), and Long-Evans Tokushima Otsuka (LETO) rats. All rat strains but OLETF expressed Fos-LI in response to CCK-8. In addition, SD rats expressed more Fos-LI in the area postrema and myenteric neurons than SLE and LETO rats. To investigate the basis for these differences, we utilized cuprolinic blue staining, which stains neuronal cell bodies, to quantify the number of myenteric neurons, and a reverse transcriptase chain polymerase reaction to measure the gene expression of CCK 1 receptor in the gut. We found that SD rats have significantly more duodenal myenteric neurons than the other strains. In addition, this strain expressed significantly higher levels of the CCK 1 gene in both the duodenum and jejunum than the other strains. In conclusion, SD rats may express more myenteric Fos-LI in response to CCK due to increased numbers of myenteric neurons or more intestinal CCK 1 receptors than the other strains of rats. D
Regulatory Peptides, 1999
Cholecystokinin (CCK) regulates intestinal motility after being released by several luminal nutrients. However the mechanism of action of CCK is still not well known. The aim of our study was to establish the mechanism of action of CCK in the rat intestine using an in vivo model and focusing on the nervous pathways involved in the response as well as type of receptors. Anesthetized rats were prepared with two strain-gauges, in duodenum and jejunum, to record circular muscle motor activity. A group of animals was also prepared with a catheter to infuse capsaicin inside the duodenum. Responses to CCK-octapeptide (CCK-8) as well as to CCK agonists were studied. CCK-8 was also infused after CCK antagonists, atropine, hexamethonium or L-nitroarginine. Results show that duodenal response to CCK-8 is excitatory although inhibitory responses can be induced by gastrin. In the jejunum, CCK-8 induces an inhibitory response that is mediated by both CCK-A and-B receptors. Excitatory responses to CCK-8 are due to stimulation of preganglionic receptors while inhibitory responses are NO mediated through stimulation of postganglionic CCK-B receptors. Capsaicin locally applied in duodenal mucosa significantly decreased CCK-8 response, whereas mucosal exposure to lidocaine completely blocked CCK-8 response. In conclusion our results show that CCK response varies along the intestine according to the predominance of excitatory or inhibitory efferent innervation. Moreover, CCK-8 actions are mediated through both extrinsic and intrinsic afferent fibres.
Cell and Tissue Research, 2001
One of the physiological functions of circulating cholecystokinin (CCK) is in the control of the pyloric sphincter and the subsequent delivery of nutrients to the small intestine. In order to identify the site(s) of action of CCK in the gastropyloric region, we performed immunohistochemistry using an antibody directed to the C-terminal region of the cholecystokinin A receptor (CCKAR). In the rat, cells that display strong CCKAR immunoreactivity and fit the morphological description of interstitial cells of Cajal (ICC) were found in the distal sphincter muscle and in the circular muscle of the proximal duodenum. Double labeling showed that these cells coexpressed vimentin, but that not all vimentinpositive cells expressed CCKAR. Confirmation that the CCKAR-expressing cells were ICC also came from kit double-labeling experiments in mice. In addition to ICC, circular smooth muscle cells at the tip of the commashaped sphincter muscle, but not elsewhere, also exhibited strong, membrane-bound CCKAR immunoreactivity. With higher antibody concentrations, the entire circular muscle displayed moderate CCKAR immunoreactivity, suggesting that circular smooth muscle cells express low levels of CCKAR. Select neurons in the myenteric ganglia near the sphincter muscle proper, the distal antrum, and proximal duodenum, as well as a few single neurons in the submucosa, also expressed strong CCKAR immunoreactivity. Finally, CCKAR-immunoreactive ICC and neurons were not specifically related to vagal afferent in-tramuscular and intraganglionic endings, and vagal afferents themselves did not exhibit any CCKAR immunoreactivity. These results suggest a role for ICC and enteric neurons in the mediation of CCK effects on pyloric sphincter pressure in addition to direct effects of the hormone on circular smooth muscle.
The Journal of Physiology, 1985
The action and mechanism of action of cholecystokinin octapeptide (CCK-8) and pentagastrin on isolated segments of guinea-pig duodenum were examined using contractility studies and by intracellular recordings made from smooth muscle cells. 2. Both CCK-8 and pentagastrin caused an excitatory contractile response. The threshold concentration ranged from 5 x 10-11 to 109 M for CCK-8 and 5 x 1010 to 10-8 M for pentagastrin. 3. The excitatory response was abolished by tetrodotoxin (3-1 x 10-6 M) and atropine (1-5 X 10-6 M) and inhibited by d-tubocurarine (up to 2-9 x 10-5 M). 4. In the presence of atropine a proportion of preparations relaxed in response to CCK-8 (nineteen of thirty-one) and pentagastrin (thirteen of seventeen). This response was only seen at high concentrations of the peptides (10-8-10-7 M) and was abolished by tetrodotoxin (3 x 10-6 M). 5. Intracellular recordings from duodenal smooth muscle revealed multiple excitatory junction potentials (e.j.p.s) in response to CCK-8 and to pentagastrin. These e.j.p.s were identical to those evoked by transmural nerve stimulation and were abolished by atropine (1.5 x 10-7 M) and by tetrodotoxin (3 x 10-6 M). Inhibitory junction potentials (i.j.p.s) were not recorded in response to the peptides except on one occasion. 6. It is suggested that CCK-8 and pentagastrin cause an increase in duodenal motility by the selective activation of excitatory pathways in the enteric nervous system.
Activation of neural cholecystokinin-1 receptors induces relaxation of the isolated rat duodenum which is reduced by nitric oxide synthase inhibitors
Brazilian Journal of Medical and Biological Research, 2006
Cholecystokinin (CCK) influences gastrointestinal motility, by acting on central and peripheral receptors. The aim of the present study was to determine whether CCK has any effect on isolated duodenum longitudinal muscle activity and to characterize the mechanisms involved. Isolated segments of the rat proximal duodenum were mounted for the recording of isometric contractions of longitudinal muscle in the presence of atropine and guanethidine. CCK-8S (EC 50 : 39; 95% CI: 4.1-152 nM) and cerulein (EC 50 : 58; 95% CI: 18-281 nM) induced a concentration-dependent and tetrodotoxin-sensitive relaxation. N ω nitro-L-arginine (L-NOARG) reduced CCK-8S-and ceruleininduced relaxation (IC 50 : 5.2; 95% CI: 2.5-18 µM) in a concentrationdependent manner. The magnitude of 300 nM CCK-8S-induced relaxation was reduced by 100 µM L-NOARG from 73 ± 5.1 to 19 ± 3.5% in an L-arginine but not D-arginine preventable manner. The CCK-1 receptor antagonists proglumide, lorglumide and devazepide, but not the CCK-2 receptor antagonist L-365,260, antagonized CCK-8Sinduced relaxation in a concentration-dependent manner. These findings suggest that CCK-8S and cerulein activate intrinsic nitrergic nerves acting on CCK-1 receptors in order to cause relaxation of the rat duodenum longitudinal muscle.