Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chromaffin granules, the secretory organelles of the neuron-like adrenal medullary chromaffin cells, have previously been shown to store and liberate neurotrophic activities that support in vitro survival of several neuron populations including those innervating the adrenal medulla. Molecules resembling fibroblast growth factor and ciliary neurotrophic factor have been identified among these activities. Since chromaffin granules store a variety of neuropeptides and many neuropeptides can have pleiotropic effects on neuronal growth and maintenance we have tested 24 different neuropeptides for their capacities to promote survival of embryonic chick ciliary, dorsal root and sympathetic ganglionic neurons. Peptides tested included several derivatives of proenkephalin (Leu- and met-enkephalin, fragments BAM 22, B, F and E), somatostatin, substance P, neuropeptide Y, neurotensin, VIP, bombesin, secretin, pancreastatin, dynorphin B, dynorphin 1-13, beta-endorphin, alpha-, beta-, and gamma-MSH. Control cultures received saturating concentrations of ciliary neurotrophic or nerve growth factor (CNTF; NGF), or no trophic supplements. At 1 x 10(-5) M leu- and met-enkephalin as well as somatostatin supported sympathetic neurons to the same extent as NGF. At the same concentrations, leu-enkephalin, the proenkephalin fragments BAM 22 and E, and somatostatin maintained about half of the dorsal root ganglionic neurons supported by NGF, but were not effective on ciliary neurons. VIP promoted the survival of approximately 50% of the ciliary and embryonic day 10 dorsal root ganglionic neurons as compared to saturating amounts of CNTF, but required the presence of non-neuronal cells in the cultures to be effective. Neurotensin (1 x 10(-5) M had a small effect on ciliary neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Screening of adrenal medullary neuropeptides for putative neurotrophic effects. 163 76

The developing fetal monkey visual cortex was studied immunocytochemically from 110-155 days post-conception in order to localize cell populations immunoreactive (ir) for gamma-aminobutyric acid, Substance P, cholecystokinin-octapeptide, somatostatin, neuropeptide Y, and proenkephalin A peptide (BAM-18). The area 17/18 border and all cortical laminae identified in the adult visual cortex were discernible from the youngest age examined. All ir-cell populations studied were present at each fetal age. However, despite a relatively adult-like cytoarchitecture, all ir-cell populations studied displayed patterns of immunostaining which were unlike those described in adult visual cortex, and showed significant changes in laminar distribution, morphology, and numbers over the time course of gestation examined. Despite the differences in the patterns of immunostaining between the fetal and adult visual cortex, ir-cell populations intrinsic to the developing visual cortex exhibited adult-like combinations of co-localized transmitters and peptides. The developing monkey cortex also contains ir-cell populations, particularly BAM-18-ir cells, which have not been detected immunocytochemically in the adult monkey cortex. Differences between the fetal and the adult ir-cell populations might be accounted for by cell death, morphological transformation, secondary migration or changes in gene expression for neurotransmitters and neuropeptides.
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PMID:Temporal sequence of neurotransmitter expression by developing neurons of fetal monkey visual cortex. 246 14

At present our knowledge of enteric peptide-containing neurons in man is limited. In this study we have used human appendices removed at surgery to examine the peptidergic innervation by immunocytochemistry, immunochemistry, and pharmacological in vitro experiments. Immunocytochemistry revealed a variety of peptide-containing nerve fiber populations in the human appendix. VIP/PHI-, VIP/PHI/NPY-, SP/NKA-, galanin-, and enkephalin-containing nerve fibers were numerous; CGRP- and GRP-containing nerve fibers were moderate in number, while only scattered NPY-, enkephalin/BAM-, and somatostatin-containing nerve fibers could be found. No CCK-, dynorphin A-, or dynorphin B-immunoreactive nerve fibers could be detected. The coexistence of VIP/PHI, SP/NKA, and enkaphalin/BAM can be anticipated from the known sequence of their respective precursors. However, the coexistence of VIP/PHI and NPY was unexpected but corroborates previous observations in other species. Interestingly, SP and CGRP did not seem to coexist in nerve fibers of the human appendix. Immunochemistry (RIA and HPLC) confirmed the presence of VIP, NPY, SP, galanin, CGRP, GRP, enkephalin, and somatostatin. Motor activity studies suggest that acetylcholine plays a major role in the electrically evoked contractions, since atropine suppressed these contractions. Galanin (10(-8)-10(-6) M) and GRP (10(-9)-10(-7) M) caused concentration-dependent contractions that were unaffected by tetrodotoxin and thus probably reflect a direct action on smooth muscle receptors. GRP (10(-9) M) enhanced the electrically induced cholinergic contraction (to 193 +/- 24%), while met-enkephalin (10(-6) M) reduced it (to 54 +/- 6%). Both peptides failed to affect the contractile response to exogenous acetylcholine and probably act to modulate the release of acetylcholine. NPY, VIP, CGRP, SP, and somatostatin failed to induce contraction or to affect the electrically evoked contractions.
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PMID:Neuropeptides in the human appendix. Distribution and motor effects. 247 67

[Met5]-Enkephalin-, [Met5]-enkephalin-Arg6-, [Met5]-enkephalin-Arg6-Phe7-, metorphamide- and BAM 22P-like peptides could be localized in the amphibian brain by immunocytochemistry. However, a [Met5]-enkephalin-Arg6-Gly7-Leu8-like peptide could not be detected in the brain of any anuran species with an antiserum that was capable of detecting this octapeptide in mammalian brain. A synenkephalin-like peptide also could not be detected in the anuran brain with an antiserum that was capable of detecting the antigen in bovine and porcine brain. Although the intensity of proenkephalin-like immunoreactivity depended on the antiserum used, its distribution appeared to be identical with all of the effective antisera. Antisera directed against somatostatin and corticotropin-releasing factor stained perikarya, nerve fibers and terminals in the anuran brain with a distribution that was different from antisera directed against proenkephalin-derived peptides. The distribution of proenkephalin-containing perikarya and nerve fibers in the regions of the anuran brain selected for study showed many similarities to the distribution of proenkephalin-containing perikarya and nerve fibers in the same regions of the amniote brain.
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PMID:Immunocytochemical analysis of proenkephalin-derived peptides in the amphibian hypothalamus and optic tectum. 311 68

The colocalization of acetylcholine (ACh) and neuropeptides (e.g., substance P and enkephalins) in the splanchnic nerve terminals suggests that these compounds might interact to modulate adrenal catecholamine release. Use has been made of primary monolayer and suspension cultures of bovine adrenal chromaffin cells to investigate postsynaptic receptor interactions between acetylcholine and a number of neuropeptides endogenous to the adrenal medulla and splanchnic nerve. The cells have both nicotinic and muscarinic acetylcholine receptors, but only the nicotinic receptors stimulate catecholamine release. Substance P, somatostatin, and the enkephalins all produced an inhibition of the ACh-evoked secretion of catecholamines, but their potency ranged over 100-fold. Substance P was the most potent with a mean inhibitory concentration (IC50) of 10(-6) M and Leu-enkephalin the least potent with an IC50 greater than 10(-4) M. These pharmacological effects were monitored conveniently by measuring the release of [3H]norepinephrine preloaded into the cells or alternatively, "on-line" by measuring ATP released into an incubation medium containing luciferin and firefly tail extract (luciferase). Of interest, the endogenous enkephalin heptapeptide (Met-enkephalin Arg6-Phe7) and "big" Met-enkephalin (BAM- 22P ) were some 100-fold more effective than Leu- or Met-enkephalin at inhibiting the nicotinic secretin of catecholamines, suggesting that a unique opiate receptor may be involved. Substance P had two distinct actions on the nicotinic response: (1) substance P inhibited acetylcholine-induced release of catecholamines; and (2) substance P protected against acetylcholine-induced desensitization of catecholamine release. With regard to (1), substance P inhibited the secretion of catecholamines and ATP evoked by acetylcholine or nicotine but not that evoked by K+ or veratridine, nor did substance P by itself affect secretion. Substance P appeared to interact with a regulatory site on the acetylcholine receptor - ionophore complex. Substance P receptors on chromaffin cells have similar structural requirements for activation as do substance P receptors in other substance P responsive tissues. With regard to (2), substance P (greater than 5 X 10(-6) M) completely protected against desensitization of catecholamine release produced by acetylcholine (greater than 10(-4) M) or nicotine (greater than 2.5 X 10(-6) M) with no effect on K+-induced desensitization.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Receptors and receptor modulation in cultured chromaffin cells. 620 33

Peptide sequence analysis and cDNA cloning indicate that a previously described mouse arginine-specific dibasic cleaving enzyme (dynorphin converting enzyme) [Csuhai et al. (1995) Biochemistry 34, 12411] is the homologue of N-arginine dibasic convertase (NRDc) isolated from rat testis [Chesneau et al. (1994) J. Biol. Chem. 269, 2056]. A mouse NRDc cDNA exhibited 98% amino acid identity with the rat cDNA. However, within a 74 residue acidic stretch, this identity drops to 82%. Likewise, the corresponding acidic stretch of human NRDc is only 73% identical with that of rat NRDc. To reconcile previously observed kinetic differences between rat and mouse NRDc, the hydrolysis of peptide substrates by the rat, human, and mouse enzymes was compared using phosphate and Tris as buffers. Although the three NRDc's behaved similarly, Tris had a pronounced effect on the kinetics of peptide hydrolysis. With BAM-8, alpha-neoendorphin, and dynorphin B as substrates, Tris increased KM up to 40-fold with little change in Vmax, while with dynorphin A or somatostatin 28 as substrate, Tris caused a decrease in KM of up to 100 fold, again with only a modest change in Vmax. Other amines, including the polyamines putrescine, spermidine, and spermine, all affected NRD convertase activity. It is proposed that amines bind to the acidic stretch found in NRDc, and that quantitative differences in the sensitivity to amines between the rat, mouse, and human enzymes can be at least partially accounted for by differences in their acidic stretch. The role of polyamines as physiological modulators of N-arginine dibasic convertase is considered.
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PMID:Regulation of N-arginine dibasic convertase activity by amines: putative role of a novel acidic domain as an amine binding site. 952 98