Henry Khachaturian | National Institutes of Health (original) (raw)
Papers by Henry Khachaturian
Journal of Comparative Neurology, Jun 22, 1985
By using a combined technique of immunocytochemistry and 13H]thymidine autoradicgraphy, we have d... more By using a combined technique of immunocytochemistry and 13H]thymidine autoradicgraphy, we have determined the "birth date" of opioid peptide-containing neurons in several hypothalamic nuclei and regions. These include proopiomelanocortin (POMC) neurons (represented by ACTH immunoreactivity) in the arcuate nucleus; dynorphin A neurons in the supraoptic and paraventrjcular nuclei and the lateral hypothalamic area; and leuenkephalin neurons in the periventricular, ventromedial, and medial mammillary nuclei, 3s well as in preoptic and perifornical areas. Arcuate POMC neurons were born very early in embrymic development, with peak heavy [3H]thymidine nuclear labelling occurring on embryonic day E12. Supraoptic and paraventricular dynorphin A neurons were also labelled relatively early (peak at E13). The lateral hypothalamic dynorphin A neurons showed peak heavy labelling also on day E12. By contrast, leu-enkephalin neurons in the periventricular nucleus and medial preoptic area exhibited peak heavy nuclear labeiling on day E14. Furthermore, perifornical and ventromedial leu-enkephalin neurons were also born relatively early (peak on days E l 2 and E13, respectively). However, the leu-enkephalin neurons in the medial mammillary nucleus were born the latest of all cell groups studied (i.e., peak at E15). The results indicate a differential genesis of these opioid peptide-containing neuronal groups in different hypothalamic nuclei and regions.
Peptides, Feb 1, 1984
of the catecholamine innervathin of the supraoptic nucleus in the Brattleboro rat. PEPTIDES 5: Su... more of the catecholamine innervathin of the supraoptic nucleus in the Brattleboro rat. PEPTIDES 5: Suppl 1,151-155, 1984.--The ontogenetic development
Trends in Neurosciences, 1985
The amzno acid sequences of the three endogenous opzoid peptzde precursors are known, and the ana... more The amzno acid sequences of the three endogenous opzoid peptzde precursors are known, and the anatomical distribution of the opiozd peptzdes has been studied extensively This report summarizes these anatomical studzes and looks at the problems that result from the biochemical relatedness of the precursors We also discuss the relatzonshzp of opzozd systems to opzoid receptors, and the use of anatomical studies to derive new hypotheses of opzozd function and provide dynamic measures of opzoid neural actzvity, especially via specific mRNA quantitation_
Life Sciences, Feb 1, 1983
Extracts of the anterior lobe and intermediate lobe of postnatal (P) (Day PI, P7, P14, P21, P28, ... more Extracts of the anterior lobe and intermediate lobe of postnatal (P) (Day PI, P7, P14, P21, P28, P35, P42) and adult male Spraque-Dawley rats were analyzed by both a Beta-endorphin (B-END) radioimmunoassay and a radioimmunoassay for N-acetyl-B-END. In the anterior lobe, on PI, less than 2% of the adult level of B-END was present. By P42 this level had increased to 21% of adult levels. In the intermediate lobe, on PI, the B-END levels were less than 0.1% of the adult level, and by P42 this level approached approximately 45% of the adult levels. N-acetylated B-END was identified in both anterior lobe and intermediate lobe from PI through adulthood. In the anterior lobe at PI, N-acetyl-B-END immunoreactivity contributes approximately 25% of the total B-END immunoreactivity.
Neuropeptides, Feb 1, 1985
AFlsTRAcr Beta-endorphin (B-END) like imnunoreactivity (i.r.) levels were measured by radioimnuno... more AFlsTRAcr Beta-endorphin (B-END) like imnunoreactivity (i.r.) levels were measured by radioimnunoassay in the medulla oblongata of developing rats on postnatal ages Pl-P42 at 7 day intervals, and in adult rats. Fran Pl to P42, B-END i.r. increased fran 77.0 + 1.3 fm to 900.0 + 21.6 fm per medulla region (Mean + S.E.M.) . Adult levels of B-END i.r. were F52.0 + 17.0 fm per medulla region, When B-END i.r. was determined per unit protein during this developmental period, a statistically significant change in levels was noted. B-END i.r. dropped fran Pl to P7, and then increased fran P7 to P14 (P<O.Ol). Fran P14 through adult, levels did not change significantly. Despite a "drop-out" in the observed irnaunostaining of B-END neurons in caudal medulla (perikarya in the nucleus tractus solitarius) at ~21, radioiaummoassayable levels of this peptide renained constant fran P21 through adult per unit protein.
![Research paper thumbnail of Pharmacological and anatomical evidence of selective [mu], [delta], and [chi] opioid receptor binding in rat brain](https://attachments.academia-assets.com/49689216/thumbnails/1.jpg)
](
In Situ Hybridization in Brain, 1986
Trends in Neurosciences, 1985
The amzno acid sequences of the three endogenous opzoid peptzde precursors are known, and the ana... more The amzno acid sequences of the three endogenous opzoid peptzde precursors are known, and the anatomical distribution of the opiozd peptzdes has been studied extensively This report summarizes these anatomical studzes and looks at the problems that result from the biochemical relatedness of the precursors We also discuss the relatzonshzp of opzozd systems to opzoid receptors, and the use of anatomical studies to derive new hypotheses of opzozd function and provide dynamic measures of opzoid neural actzvity, especially via specific mRNA quantitation_
Trends in Neurosciences, 1988
There is a wide body of evidence to suggest the existence of at least three distinct opioid recep... more There is a wide body of evidence to suggest the existence of at least three distinct opioid receptor types in the CNS, referred to as ~, 6, and K. This paper reviews some of the findings that have led to this conclusion and the anatomical distributions of these sites in the rat brain. Their relation to the opioid peptides and some of the proposed functions mediated by these receptor systems are also discussed.
Science, 1982
A study of the anatomical distribution of the endogenous opioid dynorphin in rat brain showed tha... more A study of the anatomical distribution of the endogenous opioid dynorphin in rat brain showed that the peptide is localized in a widespread system with multiple cell groups and projections. This network is revealed by the use of multiple antiserums against dynorphin and can be distinguished from the system containing methionine-enkephalin and leucine-enkephalin, which is mapped by the use of antiserums against the enkephalins and biosynthetically related peptides in the adrenal. It thus appears that the brain contains at least three separate opioid neuronal networks: an enkephalin family with components similar to those found in the adrenal, a beta-endorphin family, and a dynorphin family.
Proceedings of the National Academy of Sciences, 1983
It is known that the opioid peptide dynorphin A has a broad distribution throughout the neuraxis.... more It is known that the opioid peptide dynorphin A has a broad distribution throughout the neuraxis. Recent biochemical studies have extended the sequence of dynorphin A by 15 amino acids to include another [Leu]enkephalin-containing peptide known as dynorphin B. These sequence data.have been validated by the elucidation of the structure of the hypothalamic mRNA coding for a-and (-neo-endorphin, dynorphin A, and dynorphin B. Using specific antisera directed against each of the three opioid peptides, we have studied their cellular distribution in rat brain. Their distribution patterns are extremely similar, if not identical. Furthermore, all three peptide immunoreactivities can be localized to the same cells in five nuclear groups throughout the brainstem--the. supraoptic nucleus, the paraventricular nucleus, a group of cells in the lateral hypothalamic area, the nucleus parabrachialis, and the nucleus tractus solitarius. The sequence of a common precursor for dynorphin A, B, and a-and f-neoendorphin was deduced from hypothalamic mRNA. The ability to localize all three peptides together within cells in widely placed nuclei strongly supports the use ofthe same biosynthetic precursor for the neo-endorphin and dynorphin peptides in other parts of the central nervous system as-well.
Peptides, 1980
Abstract Characteristics of central endocrine neurons and their catecholaminergic afferent innerv... more Abstract Characteristics of central endocrine neurons and their catecholaminergic afferent innervation patterns during the aging process were examined in the Fischer 344 rat using a combined histofluorescence-immunocytochemical approach. Staining of peptidergic ...
Peptides, 1982
immunocytochemisto, in the rat central nervous system. PEPTIDES 3(6) 941-954, 1982.--The distribu... more immunocytochemisto, in the rat central nervous system. PEPTIDES 3(6) 941-954, 1982.--The distribution ofdynorphin in the central nervous system was investigated in rats pretreated with relatively high doses (3(10--400/zg) of colchicine administered intracerebroventricularly. To circumvent the problems of antibody cross-reactivity, antisera were generated against different portions as well as the full dynorphin molecule (i.e., residues 1-13, 7-17, or 1-17). For comparison, antisera to [Leu]enkephalin (residues 1-5) were also utilized. Dynorphin was found to be widely distributed throughout the neuraxis. lmmunoreactive neuronal perikarya exist in hypothalamic magnoceUular nuclei, periaqueductal gray, scattered reticular formation sites, and other brain stem nuclei, as well as in spinal cord. Additionally, dynorphin-positive fibers or terminals occur in the cerebral cortex, olfactory bulb, nucleus accumbens, caudate-putamen, globus pallidus, hypothalamus, substantia nigra, periaqueductal gray, many brain stem sties, and the spinal cord. In many areas studied, dynorphin and enkephalin appeared to form parallel but probably separate anatomical systems. The results suggest that dynorphin occurs in neuronal systems that are immunocytochemically distinct from those containing other opioid peptides.
Peptides, 1984
of the catecholamine innervathin of the supraoptic nucleus in the Brattleboro rat. PEPTIDES 5: Su... more of the catecholamine innervathin of the supraoptic nucleus in the Brattleboro rat. PEPTIDES 5: Suppl 1,151-155, 1984.--The ontogenetic development
Peptides, 1985
Combined autoradiographic-immunocytochemical analysis of opioid receptors and opioid peptide neur... more Combined autoradiographic-immunocytochemical analysis of opioid receptors and opioid peptide neuronal systems in brain. PEPTIDES 6: Suppl. 1, 37--47, 1985.--Using adjacent section autoradiography-immunocytochemistry, the distribution of [3H]naloxone binding sites was studied in relation to neuronal systems containing [Leu]enkephalin, dynorphin A, or/3-endorphin immunoreactivity in rat brain. Brain sections from formaldehyde-perfused rats show robust specific binding of [3H]naloxone, the pharmacological ~-like) properties of which appear unaltered. In contrast, specific binding of the 8 ligand [3H]D-AlaZ,D-LeuS-enkephalin was virtually totally eliminated as a result of formaldehyde perfusion. Using adjacent section analysis, we have noted associations between [3H]naloxone binding sites and one, two, or all three opioid systems in different brain regions; however, in some areas, no apparent relationship could be observed. Within regions, the relationship was complex; for example, in caudate-putamen, patches ofopioid receptors did not correspond to the distribution of enkephalin immunoreactivity, but there was a correspondence between subeallosal streaks of binding sites and enkephalin. The complexity of the association between [3H]naloxone binding sites and the multiple opioid systems, and previous reports of colocalization of Ix and K receptors in rat brain, are inconsistent with a simple-one-to-one relationship between a given opioid precursor and opioid receptor subtype. Instead, since differential processing of the three precursors gives rise to peptides of varying receptor subtype potencies and selectivities, the multiple peptide-receptor relationships may point to a key role of post-translational processing in determining the physiological consequences of opioid neurotransmission.
Peptides, 1985
Prodynorphin peptide immunocytoehemistrv in rhesus monkey brain. PEPTIDES 6: Suppl. 2, 155-166, 1... more Prodynorphin peptide immunocytoehemistrv in rhesus monkey brain. PEPTIDES 6: Suppl. 2, 155-166, 1985. --The present study describes the immunocytochemical distribution of peptides derived from the prodynorphin precursor in the brain of the rhesus monkey (Macaea mulatta). Animals were treated with colchicine (intracerebroventricularly) prior to perfusion to enhance the observation of perikaryal immunoreactivity. Using antisera generated against dynorphin A(1-17), dynorphin B(1-13), and prodynorphin(186-208) (or bridge peptide), the anatomical distribution of dynorphin systems was mapped. The results indicate a widespread neuronal localization ofimmunoreactivity from the cerebral cortex to the caudal medulla. Anti-dynorphin B and anti-bridge peptide sera proved useful for the demonstration of neuronal perikarya, while the dynorphin A antiserum was best for localizing terminal projection fields. Immunoreactive perikarya are located in numerous brain loci, including the cingulate cortex, caudate nucleus, amygdala, hypothalamus (especially the magnocellular nuclei), thalamus, substantia grisea centralis, parabrachial nucleus, nucleus tractus solitarius, and other nuclei. In addition, fiber and terminal immunoreactivity are seen in varying densities in the striatum and pallidum, substantia innominata, hypothalamus, substantia nigra pars reticulata, parabrachial nucleus, spinal trigeminal nucleus, and other areas. The distribution of prodynorphin peptides in the brain of the monkey is similar to that described for the rat brain; however, significant differences also exist. Other interspecies differences in the anatomy of prodynorphin and proenkephalin neuronal systems in the monkey and human brain are further discussed.
Peptides, 1988
effects on beta-endorphm and alpha-MSH m the hypothalamus and caudal medulla PEPTIDES 9(4) 689-69... more effects on beta-endorphm and alpha-MSH m the hypothalamus and caudal medulla PEPTIDES 9(4) 689-695, 1988.--Monosodmm glutamate (MSG) was given to neonatal male rats to determine its effects on neurons contmnlng beta-endorphm (B-END) and alpha-melanocyte stimulating hormone (a-MSH) within the basal hypothalamus (arcuate nucleus) and caudal medulla [nucleus tractus sohtarlus (NTS)I and on the levels of B-END and c~-MSH within these areas. Immunocytochemlcal studies demonstrated a reduction in the number of cells within the medial hypotbalamlc area (arcuate nucleus) among MSG-treated ammals versus saline controls. MSG did not reduce the number of cell bodies within the caudal medulla (NTS). MSG slgmficantly reduced B-END and a-MSH lmmunoreactive levels m the basal hypothalamus as determined by radmlmmunoassay. Whereas a slgmficant reduction in the level of B-END occurred in the ventral caudal medulla (VCM), none occurred in the dorsal caudal medulla (DCM) In contrast, levels of a-MSH increased slgmficantly m the DCM among animals receiving MSG compared to control animals. This study documents the contribution of beta-endorphm contmnmg neurons of the basal hypothalamus to areas of the caudal medulla. The effect of MSG on beta-endorphln and a-MSH neurons in these areas and their differentml effects on levels in the caudal medulla areas raises questmns about the sites of ongm of these pept~des.
Journal of Comparative Neurology, Jun 22, 1985
By using a combined technique of immunocytochemistry and 13H]thymidine autoradicgraphy, we have d... more By using a combined technique of immunocytochemistry and 13H]thymidine autoradicgraphy, we have determined the "birth date" of opioid peptide-containing neurons in several hypothalamic nuclei and regions. These include proopiomelanocortin (POMC) neurons (represented by ACTH immunoreactivity) in the arcuate nucleus; dynorphin A neurons in the supraoptic and paraventrjcular nuclei and the lateral hypothalamic area; and leuenkephalin neurons in the periventricular, ventromedial, and medial mammillary nuclei, 3s well as in preoptic and perifornical areas. Arcuate POMC neurons were born very early in embrymic development, with peak heavy [3H]thymidine nuclear labelling occurring on embryonic day E12. Supraoptic and paraventricular dynorphin A neurons were also labelled relatively early (peak at E13). The lateral hypothalamic dynorphin A neurons showed peak heavy labelling also on day E12. By contrast, leu-enkephalin neurons in the periventricular nucleus and medial preoptic area exhibited peak heavy nuclear labeiling on day E14. Furthermore, perifornical and ventromedial leu-enkephalin neurons were also born relatively early (peak on days E l 2 and E13, respectively). However, the leu-enkephalin neurons in the medial mammillary nucleus were born the latest of all cell groups studied (i.e., peak at E15). The results indicate a differential genesis of these opioid peptide-containing neuronal groups in different hypothalamic nuclei and regions.
Peptides, Feb 1, 1984
of the catecholamine innervathin of the supraoptic nucleus in the Brattleboro rat. PEPTIDES 5: Su... more of the catecholamine innervathin of the supraoptic nucleus in the Brattleboro rat. PEPTIDES 5: Suppl 1,151-155, 1984.--The ontogenetic development
Trends in Neurosciences, 1985
The amzno acid sequences of the three endogenous opzoid peptzde precursors are known, and the ana... more The amzno acid sequences of the three endogenous opzoid peptzde precursors are known, and the anatomical distribution of the opiozd peptzdes has been studied extensively This report summarizes these anatomical studzes and looks at the problems that result from the biochemical relatedness of the precursors We also discuss the relatzonshzp of opzozd systems to opzoid receptors, and the use of anatomical studies to derive new hypotheses of opzozd function and provide dynamic measures of opzoid neural actzvity, especially via specific mRNA quantitation_
Life Sciences, Feb 1, 1983
Extracts of the anterior lobe and intermediate lobe of postnatal (P) (Day PI, P7, P14, P21, P28, ... more Extracts of the anterior lobe and intermediate lobe of postnatal (P) (Day PI, P7, P14, P21, P28, P35, P42) and adult male Spraque-Dawley rats were analyzed by both a Beta-endorphin (B-END) radioimmunoassay and a radioimmunoassay for N-acetyl-B-END. In the anterior lobe, on PI, less than 2% of the adult level of B-END was present. By P42 this level had increased to 21% of adult levels. In the intermediate lobe, on PI, the B-END levels were less than 0.1% of the adult level, and by P42 this level approached approximately 45% of the adult levels. N-acetylated B-END was identified in both anterior lobe and intermediate lobe from PI through adulthood. In the anterior lobe at PI, N-acetyl-B-END immunoreactivity contributes approximately 25% of the total B-END immunoreactivity.
Neuropeptides, Feb 1, 1985
AFlsTRAcr Beta-endorphin (B-END) like imnunoreactivity (i.r.) levels were measured by radioimnuno... more AFlsTRAcr Beta-endorphin (B-END) like imnunoreactivity (i.r.) levels were measured by radioimnunoassay in the medulla oblongata of developing rats on postnatal ages Pl-P42 at 7 day intervals, and in adult rats. Fran Pl to P42, B-END i.r. increased fran 77.0 + 1.3 fm to 900.0 + 21.6 fm per medulla region (Mean + S.E.M.) . Adult levels of B-END i.r. were F52.0 + 17.0 fm per medulla region, When B-END i.r. was determined per unit protein during this developmental period, a statistically significant change in levels was noted. B-END i.r. dropped fran Pl to P7, and then increased fran P7 to P14 (P<O.Ol). Fran P14 through adult, levels did not change significantly. Despite a "drop-out" in the observed irnaunostaining of B-END neurons in caudal medulla (perikarya in the nucleus tractus solitarius) at ~21, radioiaummoassayable levels of this peptide renained constant fran P21 through adult per unit protein.
In Situ Hybridization in Brain, 1986
Trends in Neurosciences, 1985
The amzno acid sequences of the three endogenous opzoid peptzde precursors are known, and the ana... more The amzno acid sequences of the three endogenous opzoid peptzde precursors are known, and the anatomical distribution of the opiozd peptzdes has been studied extensively This report summarizes these anatomical studzes and looks at the problems that result from the biochemical relatedness of the precursors We also discuss the relatzonshzp of opzozd systems to opzoid receptors, and the use of anatomical studies to derive new hypotheses of opzozd function and provide dynamic measures of opzoid neural actzvity, especially via specific mRNA quantitation_
Trends in Neurosciences, 1988
There is a wide body of evidence to suggest the existence of at least three distinct opioid recep... more There is a wide body of evidence to suggest the existence of at least three distinct opioid receptor types in the CNS, referred to as ~, 6, and K. This paper reviews some of the findings that have led to this conclusion and the anatomical distributions of these sites in the rat brain. Their relation to the opioid peptides and some of the proposed functions mediated by these receptor systems are also discussed.
Science, 1982
A study of the anatomical distribution of the endogenous opioid dynorphin in rat brain showed tha... more A study of the anatomical distribution of the endogenous opioid dynorphin in rat brain showed that the peptide is localized in a widespread system with multiple cell groups and projections. This network is revealed by the use of multiple antiserums against dynorphin and can be distinguished from the system containing methionine-enkephalin and leucine-enkephalin, which is mapped by the use of antiserums against the enkephalins and biosynthetically related peptides in the adrenal. It thus appears that the brain contains at least three separate opioid neuronal networks: an enkephalin family with components similar to those found in the adrenal, a beta-endorphin family, and a dynorphin family.
Proceedings of the National Academy of Sciences, 1983
It is known that the opioid peptide dynorphin A has a broad distribution throughout the neuraxis.... more It is known that the opioid peptide dynorphin A has a broad distribution throughout the neuraxis. Recent biochemical studies have extended the sequence of dynorphin A by 15 amino acids to include another [Leu]enkephalin-containing peptide known as dynorphin B. These sequence data.have been validated by the elucidation of the structure of the hypothalamic mRNA coding for a-and (-neo-endorphin, dynorphin A, and dynorphin B. Using specific antisera directed against each of the three opioid peptides, we have studied their cellular distribution in rat brain. Their distribution patterns are extremely similar, if not identical. Furthermore, all three peptide immunoreactivities can be localized to the same cells in five nuclear groups throughout the brainstem--the. supraoptic nucleus, the paraventricular nucleus, a group of cells in the lateral hypothalamic area, the nucleus parabrachialis, and the nucleus tractus solitarius. The sequence of a common precursor for dynorphin A, B, and a-and f-neoendorphin was deduced from hypothalamic mRNA. The ability to localize all three peptides together within cells in widely placed nuclei strongly supports the use ofthe same biosynthetic precursor for the neo-endorphin and dynorphin peptides in other parts of the central nervous system as-well.
Peptides, 1980
Abstract Characteristics of central endocrine neurons and their catecholaminergic afferent innerv... more Abstract Characteristics of central endocrine neurons and their catecholaminergic afferent innervation patterns during the aging process were examined in the Fischer 344 rat using a combined histofluorescence-immunocytochemical approach. Staining of peptidergic ...
Peptides, 1982
immunocytochemisto, in the rat central nervous system. PEPTIDES 3(6) 941-954, 1982.--The distribu... more immunocytochemisto, in the rat central nervous system. PEPTIDES 3(6) 941-954, 1982.--The distribution ofdynorphin in the central nervous system was investigated in rats pretreated with relatively high doses (3(10--400/zg) of colchicine administered intracerebroventricularly. To circumvent the problems of antibody cross-reactivity, antisera were generated against different portions as well as the full dynorphin molecule (i.e., residues 1-13, 7-17, or 1-17). For comparison, antisera to [Leu]enkephalin (residues 1-5) were also utilized. Dynorphin was found to be widely distributed throughout the neuraxis. lmmunoreactive neuronal perikarya exist in hypothalamic magnoceUular nuclei, periaqueductal gray, scattered reticular formation sites, and other brain stem nuclei, as well as in spinal cord. Additionally, dynorphin-positive fibers or terminals occur in the cerebral cortex, olfactory bulb, nucleus accumbens, caudate-putamen, globus pallidus, hypothalamus, substantia nigra, periaqueductal gray, many brain stem sties, and the spinal cord. In many areas studied, dynorphin and enkephalin appeared to form parallel but probably separate anatomical systems. The results suggest that dynorphin occurs in neuronal systems that are immunocytochemically distinct from those containing other opioid peptides.
Peptides, 1984
of the catecholamine innervathin of the supraoptic nucleus in the Brattleboro rat. PEPTIDES 5: Su... more of the catecholamine innervathin of the supraoptic nucleus in the Brattleboro rat. PEPTIDES 5: Suppl 1,151-155, 1984.--The ontogenetic development
Peptides, 1985
Combined autoradiographic-immunocytochemical analysis of opioid receptors and opioid peptide neur... more Combined autoradiographic-immunocytochemical analysis of opioid receptors and opioid peptide neuronal systems in brain. PEPTIDES 6: Suppl. 1, 37--47, 1985.--Using adjacent section autoradiography-immunocytochemistry, the distribution of [3H]naloxone binding sites was studied in relation to neuronal systems containing [Leu]enkephalin, dynorphin A, or/3-endorphin immunoreactivity in rat brain. Brain sections from formaldehyde-perfused rats show robust specific binding of [3H]naloxone, the pharmacological ~-like) properties of which appear unaltered. In contrast, specific binding of the 8 ligand [3H]D-AlaZ,D-LeuS-enkephalin was virtually totally eliminated as a result of formaldehyde perfusion. Using adjacent section analysis, we have noted associations between [3H]naloxone binding sites and one, two, or all three opioid systems in different brain regions; however, in some areas, no apparent relationship could be observed. Within regions, the relationship was complex; for example, in caudate-putamen, patches ofopioid receptors did not correspond to the distribution of enkephalin immunoreactivity, but there was a correspondence between subeallosal streaks of binding sites and enkephalin. The complexity of the association between [3H]naloxone binding sites and the multiple opioid systems, and previous reports of colocalization of Ix and K receptors in rat brain, are inconsistent with a simple-one-to-one relationship between a given opioid precursor and opioid receptor subtype. Instead, since differential processing of the three precursors gives rise to peptides of varying receptor subtype potencies and selectivities, the multiple peptide-receptor relationships may point to a key role of post-translational processing in determining the physiological consequences of opioid neurotransmission.
Peptides, 1985
Prodynorphin peptide immunocytoehemistrv in rhesus monkey brain. PEPTIDES 6: Suppl. 2, 155-166, 1... more Prodynorphin peptide immunocytoehemistrv in rhesus monkey brain. PEPTIDES 6: Suppl. 2, 155-166, 1985. --The present study describes the immunocytochemical distribution of peptides derived from the prodynorphin precursor in the brain of the rhesus monkey (Macaea mulatta). Animals were treated with colchicine (intracerebroventricularly) prior to perfusion to enhance the observation of perikaryal immunoreactivity. Using antisera generated against dynorphin A(1-17), dynorphin B(1-13), and prodynorphin(186-208) (or bridge peptide), the anatomical distribution of dynorphin systems was mapped. The results indicate a widespread neuronal localization ofimmunoreactivity from the cerebral cortex to the caudal medulla. Anti-dynorphin B and anti-bridge peptide sera proved useful for the demonstration of neuronal perikarya, while the dynorphin A antiserum was best for localizing terminal projection fields. Immunoreactive perikarya are located in numerous brain loci, including the cingulate cortex, caudate nucleus, amygdala, hypothalamus (especially the magnocellular nuclei), thalamus, substantia grisea centralis, parabrachial nucleus, nucleus tractus solitarius, and other nuclei. In addition, fiber and terminal immunoreactivity are seen in varying densities in the striatum and pallidum, substantia innominata, hypothalamus, substantia nigra pars reticulata, parabrachial nucleus, spinal trigeminal nucleus, and other areas. The distribution of prodynorphin peptides in the brain of the monkey is similar to that described for the rat brain; however, significant differences also exist. Other interspecies differences in the anatomy of prodynorphin and proenkephalin neuronal systems in the monkey and human brain are further discussed.
Peptides, 1988
effects on beta-endorphm and alpha-MSH m the hypothalamus and caudal medulla PEPTIDES 9(4) 689-69... more effects on beta-endorphm and alpha-MSH m the hypothalamus and caudal medulla PEPTIDES 9(4) 689-695, 1988.--Monosodmm glutamate (MSG) was given to neonatal male rats to determine its effects on neurons contmnlng beta-endorphm (B-END) and alpha-melanocyte stimulating hormone (a-MSH) within the basal hypothalamus (arcuate nucleus) and caudal medulla [nucleus tractus sohtarlus (NTS)I and on the levels of B-END and c~-MSH within these areas. Immunocytochemlcal studies demonstrated a reduction in the number of cells within the medial hypotbalamlc area (arcuate nucleus) among MSG-treated ammals versus saline controls. MSG did not reduce the number of cell bodies within the caudal medulla (NTS). MSG slgmficantly reduced B-END and a-MSH lmmunoreactive levels m the basal hypothalamus as determined by radmlmmunoassay. Whereas a slgmficant reduction in the level of B-END occurred in the ventral caudal medulla (VCM), none occurred in the dorsal caudal medulla (DCM) In contrast, levels of a-MSH increased slgmficantly m the DCM among animals receiving MSG compared to control animals. This study documents the contribution of beta-endorphm contmnmg neurons of the basal hypothalamus to areas of the caudal medulla. The effect of MSG on beta-endorphln and a-MSH neurons in these areas and their differentml effects on levels in the caudal medulla areas raises questmns about the sites of ongm of these pept~des.