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

The gastrointestinal and respiratory tracts contain numerous regulatory peptides produced by and released from specialised epithelial cells and the organ innervation. This complex system of endocrine cells and nerves is generally called "the diffuse neuroendocrine system". Markers are now available which permit the visualisation of the diffuse neuroendocrine system or its individual components. These include antibodies to neuron-specific enolase, chromogranin, neurofilament triplet proteins, the brain protein S100 and antibodies to a variety of regulatory peptides. Peptides present in the gut and lung innervation include: vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), galanin, substance P, calcitonin gene-related peptide (CGRP), neuropeptide tyrosine (NPY), somatostatin and cholecystokinin (the latter two are also localised to endocrine cells of the gut). Bombesin-immunoreactivity is found in nerves in the gut and in endocrine cells of the foetal/neonatal lung. Neuropeptides of the gut and lung originate either from local neurons (e.g. VIP, PHI, galanin) or extrinsic neurons localised in sensory ganglia (e.g. substance P and CGRP) or the sympathetic chain (e.g. NPY). Recent studies point to the involvement of regulatory peptides in diseases of the gut and lung. These, together with detailed distribution studies, provide supportive data on the putative role of the peptides in the control of normal bowel and respiratory functions. The gastrointestinal and respiratory tracts were within the systems investigated by Feyrter during his original observations on the existence of specialised epithelial cells with a putative regulatory function (Feyrter, 1938). These "endocrine/paracrine" cells were found to be scattered in epithelial organs throughout the body. In fact, endocrine cells of the respiratory tract are frequently referred to as "Feyrter's cells". The term "regulatory peptides" was introduced as a generic term (Polak and Bloom, 1983) after the finding that active peptides are produced both by cells of the diffuse endocrine or APUD (amine precursor uptake and decarboxylation) system (Pearse, 1983) and autonomic/sensory nerves. These peptides are released into the circulation from endocrine cells or locally from nerve terminals or paracrine cells. The concept of "gut/brain" peptides was dispelled after the findings that the respiratory tract was provided abundantly with numerous active peptides produced by and released from mucosal endocrine cells and/or the innervation.
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PMID:Regulatory peptides of the gastrointestinal and respiratory tracts. 242 59

By use of the indirect immunofluorescence technique the distribution of calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) has been analyzed in cervical and lumbar dorsal root ganglia of untreated and colchicine-treated rats. In addition, lumbar ganglia were examined 2 weeks after transection of the sciatic nerve. The occurrence of CGRP-positive cells in relation to ganglion cells containing substance P-, somatostatin-, galanin-, cholecystokinin (CCK)-, and vasoactive intestinal polypeptide (VIP)/peptide histidine isoleucin (PHI)-LI has been evaluated on consecutive sections as well as using elution-restaining and double-staining techniques. CGRP-LI was observed in many ganglion cells of all sizes ranging in diameter from 15 microns to 65 microns. Thus, this peptide occurs also in the large primary sensory neurons. In contrast to the sensory peptides described to date, CGRP-positive cells constituted up to 50% of all and 70% of the medium-sized neurons, thus being the most frequently occurring peptide in sensory neurons so far encountered. Subpulations of CGRP-positive neurons were shown to contain substance P-, somatostatin-, or galanin-LI and some CGRP-positive neurons contained both substance P- and galanin-LI. In fact, most substance P-, somatostatin- and galanin-positive cell bodies were CGRP-immunoreactive. The coexistence analysis further revealed that galanin and substance P often coexisted and that some cells contained both substance P- and somatostatin-LI, whereas no coexistence between galanin and somatostatin has as yet been seen. VIP/PHI-LI was only shown in a few cells in untreated or colchicine-treated rats. However, after transection of the sciatic nerve numerous VIP/PHI-positive cells were observed, some of which also contained CGRP-LI. The present results indicate that a CGRP-like peptide is present in a wide range of primary sensory neurons probably not related to specific sensory modalities. Often this peptide coexists with other biologically active peptides. Taken together these findings suggest that CGRP may have a generalized function.
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PMID:Primary sensory neurons of the rat showing calcitonin gene-related peptide immunoreactivity and their relation to substance P-, somatostatin-, galanin-, vasoactive intestinal polypeptide- and cholecystokinin-immunoreactive ganglion cells. 243 36

The effect of GHRH in a dose (120 micrograms) thought to produce a maximal GH response was compared with the GH response to insulin-induced hypoglycemia, iv infusion of the hypothalamic neuropeptide galanin (40 pmol/kg.min for 40 min), and a combination of GHRH and galanin in normal men. The median peak serum GH level was 29 mU/L in response to GHRH, 28.9 mU/L in response to insulin hypoglycemia, 17.3 mU/L in response to galanin, and 115.0 mU/L in response to the combination of galanin and GHRH. GH release induced by galanin was completely inhibited by a concomitant somatostatin infusion (50 pmol/kg.min). Thus, galanin increased the peak GH response to GHRH, previously thought to be one of the most powerful stimulants to GH release, more than 3-fold. Since the dose of GHRH used was thought to be maximal and since galanin is reported not to have direct effects on the pituitary, one possible mode of action of galanin would be inhibition of tonic endogenous hypothalamic somatostatin release.
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PMID:Growth hormone (GH) release in response to GH-releasing hormone in man is 3-fold enhanced by galanin. 244 73

This study examined the effects of electrically stimulating submucosal neurons in the guinea pig isolated distal colonic mucosa and determined the effects of several peptides that are present in these neurons. Electrical field stimulation of muscle-stripped segments of guinea pig distal colonic mucosa, set up in Ussing flux chambers, evoked an increase in short-circuit current (Isc), of 371 +/- 31 MicroA.cm-2. The response to electrical stimulation was abolished by tetrodotoxin and significantly reduced by serosal furosemide. Atropine reduced, but did not abolish, the neurally evoked response. Addition of neuropeptide Y and galanin to the serosal bath had no effect on baseline Isc, but both evoked a concentration-dependent decrease in the neurally evoked secretory response. Vasoactive intestinal polypeptide evoked a concentration-dependent increase in basal (unstimulated) Isc that was reduced by furosemide and unaltered by tetrodotoxin. Neuropeptide Y, but not galanin, significantly reduced the secretory responses to vasoactive intestinal polypeptide and bethanechol. Somatostatin 201-995 and human calcitonin gene-related peptide had no effect on basal Isc nor did either alter the neurally evoked response. These results suggest that acetylcholine and non-cholinergic neurotransmitter(s) stimulate chloride secretion in the guinea pig distal colonic mucosa. This neurosecretory response may be modulated by neuropeptide Y and galanin that are found within submucosal neurons.
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PMID:Neuropeptide modification of chloride secretion in guinea pig distal colon. 244 52

The developmental patterns of neurofilament triplet proteins, peptide and amine immunoreactivities were compared in motor (ventral spinal cord), sensory (dorsal spinal cord, dorsal root ganglia, epidermis), and autonomic (intermediolateral cell columns, dermis) regions in the rat and human. In the rat, neurofilament triplet proteins first appeared in motoneurones (embryonic day 13). In the youngest human fetuses studied (6 weeks), immunoreactivity was present throughout the spinal cord. Peptides and amines occurred later. Calcitonin gene-related peptide, galanin, somatostatin, neuropeptide Y and its C-flanking peptide (CPON) were the first to appear localized to motoneurones (embryonic days 15-17 rat; fetal weeks 6-14 human). Numbers of immunoreactive motoneurones decreased toward birth, but immunoreactive fibers increased in the ventral horn with enkephalin, thyrotrophin-releasing hormone, and the monoaminergic markers 5-hydroxytryptamine and tyrosine hydroxylase (all presumably of supraspinal origin) the last to appear perinatally. In the dorsal horn, particularly in the rat, a transient expression of substance P-, somatostatin-, and neuropeptide Y/CPON-immunoreactive cells was detected (embryonic days 15-17). A pronounced increase of calcitonin gene-related peptide-, galanin-, somatostatin- and substance P- immunoreactive fibers was found perinatally in both species. This coincided with an increased detection of cells in the dorsal root ganglia containing these peptides and the earliest appearance of calcitonin gene-related peptide-, somatostatin-, and substance P-immunoreactive fibers in the rat epidermis. Few antigens were localized to the intermediolateral cell columns before embryonic day 20 (rat), fetal week 20 (human), with thyrotrophin-releasing hormone-, 5-hydroxytryptamine-, tyrosine hydroxylase-, and vasoactive intestinal polypeptide-immunoreactive nerves appearing perinatally. In the rat dermis, tyrosine hydroxylase-immunoreactive fibers (sympathetic fibers) and fibers immunoreactive for neuropeptide Y/CPON and vasoactive intestinal polypeptide were detected from postnatal day 1. In conclusion, 1) peptide and amine immunoreactivity develops in motor before sensory or autonomic regions, 2) many peptide-containing cells are transient in fetal life, and 3) central terminals of dorsal root ganglion cells express peptides before terminals in the skin.
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PMID:Ontogeny of peptide- and amine-containing neurones in motor, sensory, and autonomic regions of rat and human spinal cord, dorsal root ganglia, and rat skin. 244 34

An increasing number of messengers have recently been found to coexist with growth hormone (GH)-releasing factor (GRF) in hypothalamic neurons. In view of a possible cosecretion of these substances with GRF into the portal circulation, the effect of synthetic rat hypothalamic GRF(1-43) alone, or together with dopamine (DA), L-dopa, gamma-aminobutyric acid (GABA), neurotensin (NT) or galanin (GAL) on GH release was investigated by using dispersed rat anterior pituitary cells in monolayer culture. GRF in concentrations of 10(-16)-10(-7) M stimulated GH release from somatotrophs in a dose-related manner. DA (10(-5) M), L-dopa (10(-8) and 10(-5) M) and GABA (10(-9) and 10(-5) M) did not affect basal GH release, whereas DA, but not L-dopa or GABA, significantly suppressed GRF-induced GH secretion. However, the inhibitory effect of DA on GRF-stimulated GH secretion was not observed in the presence of somatostatin (10(-6) M). NT (10(-6) M) and GAL (10(-6) M) did not change basal GH release. GAL, but not NT, inhibited GRF-stimulated GH release, but the addition of NT abolished the inhibitory actions of both GAL and DA. These results indicate that substances, probably coreleased with GRF from the same nerve endings, interact in the regulation of GH secretion at the pituitary level.
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PMID:Influence of coexisting hypothalamic messengers on growth hormone secretion from rat anterior pituitary cells in vitro. 244 97

The mechanism underlying the GH-releasing effect of galanin (GAL), a novel 29-amino acid peptide, was investigated in the neonatal rat. The effect of galanin was compared to that of clonidine (CLO), a drug known to release GH via endogenous GHRF. GAL administration (5-25 micrograms/kg BW, sc) induced in 10-day-old pups a clear-cut and dose-related rise in plasma GH 15 min postinjection. CLO (50-450 micrograms/kg BW, sc) induced a marked rise in plasma GH, but no dose-related effect was evident. Inhibition of hypothalamic norepinephrine and epinephrine biosynthesis by DU-18288 (6 mg/kg BW, ip) or selective inhibition of epinephrine biosynthesis by SKF-64139 (50 mg/kg BW, ip) completely abolished the GH-releasing effect of GAL (25 micrograms/kg, sc), but left unaltered the GH rise induced by CLO (150 micrograms/kg, sc). Passive immunization with an anti-GHRF serum decreased basal GH levels and prevented the GH-releasing effect of either GAL or CLO, whereas in pups pretreated with an antisomatostatin serum, CLO, but not GAL, increased the already elevated plasma GH titers. In all these data indicate that in the infant rat 1) GAL is a potent GH secretagogue; 2) the action of GAL is not exerted directly on GHRF- or somatostatin-secreting structures, but requires the intervention of catecholaminergic neurons; 3) the GH-releasing effect of GAL is ultimately exerted via GHRF release, although a mechanism operating to inhibit hypothalamic somatostatin release cannot be ruled out; and 4) differently from GAL, CLO releases GH via postsynaptic stimulation of GHRF-secreting neurons.
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PMID:Epinephrine mediates the growth hormone-releasing effect of galanin in infant rats. 244 42

Galanin is a 29 amino acid peptide, initially isolated from the porcine small intestine. The peptide has been shown to occur in intrapancreatic nerves in close association to the islets. Its effects on islet hormone secretion and its possible mechanisms behind these effects are reviewed. Galanin has been shown to inhibit basal and stimulated insulin secretion both in vivo and in vitro under a variety of experimental conditions. The peptide has also been shown to inhibit somatostatin secretion and the secretion of pancreatic polypeptide (PP). With regard to glucagon secretion, however, results in the literature are not consistent since both stimulatory and inhibitory effects have been reported. A direct interaction with the pancreatic beta-cells has been proposed behind its inhibitory action on insulin secretion, since galanin inhibits insulin secretion from isolated beta-cells from obese, hyperglycaemic, mice. Galanin has thereby also been shown to induce repolarization and to reduce the free Ca2+ concentration, [Ca2+]i. The reduction in [Ca2+]i is probably not due to a direct interference with the voltage-activated Ca2+ channels, since there is no effect of galanin when these channels are opened by depolarization induced by high concentrations of K+. Instead, preliminary studies indicate that galanin activates the K+ channels that are regulated by ATP, in turn inducing a repolarization-induced reduction in [Ca2+]i resulting in reduced insulin secretion. However, the possibility that galanin inhibits the insulin secretory mechanism at a step distal to the regulation of cytoplasmic free Ca2+ concentration should not be overlooked.
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PMID:Galanin and the endocrine pancreas. 245 47

Nerves containing galanin immunoreactivity have been shown to be present in the stomach and pancreas. The present experiments were designed to test the effect of galanin on the release of gastric somatostatin-like immunoreactivity (SLI) and immunoreactive gastrin (IR-G), pancreatic SLI and immunoreactive insulin (IR-I) from the isolated perfused rat stomach and pancreas respectively. Galanin (2 X 10(-10)-5 X 10(-8) M) inhibited gastric SLI and IR-G release dose dependently. At a concentration of 10(-8) M, galanin also suppressed IR-I release stimulated by gastric inhibitory polypeptide (2 X 10(-10) M) in the presence of 8.9 X 10(-3) M glucose. Pancreatic SLI release under this condition was not altered. Thus the present study suggests that galanin might be involved in the neural regulation of gastric and pancreatic endocrine secretions.
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PMID:Effect of galanin on endocrine secretions from the isolated perfused rat stomach and pancreas. 245 Jul 59

In five healthy normal male volunteers, pretreatment with the cholinergic muscarinic antagonist pirenzepine (30 mg i.v.) almost abolished the growth hormone (GH) response to a maximal dose (120 micrograms i.v.) of growth hormone-releasing hormone (GHRH) (GH response at 40 min 5.6 + 1.3 mU/l with GHRH and pirenzepine vs 40.8 +/- 5.3 mU/l with GHRH alone, P less than 0.02). Concomitant i.v. infusion of galanin (40 pmol/kg/min) with pirenzepine not only restored but significantly potentiated the GH response to GHRH (GH at 40 min 72.2 +/- 10.5 mU/l, P less than 0.001 vs GHRH and pirenzepine, P less than 0.02 vs GHRH alone). Previous studies have proposed that cholinergic pathways control GH release via somatostatin and this study suggests that galanin may act by modulating hypothalamic somatostatinergic tone either directly or, possibly, by facilitating cholinergic neurotransmission.
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PMID:Galanin abolishes the inhibitory effect of cholinergic blockade on growth hormone-releasing hormone-induced secretion of growth hormone in man. 245 Sep 44


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