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 study of neurotransmitter receptors aids in the understanding of the normal anatomy, pharmacology, therapeutics and pathophysiology of disease processes involving the basal ganglia. Receptors may be studied in vitro by homogenate binding experiments, enzyme analysis or quantitative autoradiography and in vivo with positron emission tomography. In the substantia nigra (SN), receptors have been identified for somatostatin, neurotensin, substance P, glycine, benzodiazepine and GABA, opiates, dopamine, angiotensin converting enzyme (ACE) and serotonin. The striatum has receptors for dopamine, GABA and benzodiazepines, acetylcholine, opiates, substance P, glutamate and cholecystokinin. GABA and benzodiazepine receptors are also located in the globus pallidus. In Parkinson's disease, striatal dopamine D-2 receptors are elevated in patients that have not received L-DOPA therapy. This supersensitivity is reversed with agonist therapy. Muscarinic binding to cholinergic receptors seems to correlate with dopamine receptors. Delta opiate receptors are increased in the caudate and mu binding is reduced in the striatum. In the SN of patients with Parkinson's disease, there is reduced binding of somatostatin, neurotensin, mu and kappa opiates, benzodiazepine and GABA and glycine. In Huntington's disease, there is reduced binding of GABA and benzodiazepines, dopamine, acetylcholine, glutamate and CCK. There is increased binding of GABA in both the SN and globus pallidus. Glycine binding is increased in the substantia nigra and ACE is reduced.
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PMID:Receptors in the basal ganglia. 282 9

The effects of a cyclic hexapeptide analog of somatostatin, [cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe)] (cyclo-SS), administered intravenously (iv) or instilled into the duodenum (id) on the pancreatic response to endogenous (meal and duodenal acidification) and exogenous (secretin, CCK) stimulants were compared in five dogs with esophageal, gastric, and pancreatic fistulae. Cyclo-SS given iv in graded doses against a constant background stimulation with secretin caused a similar and dose-dependent inhibition of pancreatic HCO3 and protein secretion being about twice as potent as somatostatin-14 (SS-14). Cyclo-SS, whether applied topically to the duodenal mucosa in a dose of 1 microgram/kg or given iv at a dose of 0.5 microgram/kg-hr, resulted in a similar inhibition of pancreatic secretion induced by feeding a meat meal, sham-feeding, duodenal acidification, or infusion of secretin or CCK. The inhibition of pancreatic secretion by cyclo-SS was due in part to direct inhibitory action on the exocrine pancreas as well as to the suppression of the release of secretin, insulin, and pancreatic polypeptide. It is concluded that cyclo-SS is a more potent inhibitor of pancreatic secretion than SS-14 and that it is active when administered both parenterally and intraduodenally.
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PMID:Effects of cyclic hexapeptide analog of somatostatin on pancreatic secretion in dogs. 285 53

A large number of antisera to regulatory vertebrate peptides was tested immunocytochemically on the nervous system of the Colorado potato beetle to further characterize the peptidergic cells of the neuro-endocrine system and to reveal cells participating in endocrine control mechanisms. Neurons, neurosecretory cells, axons and axon terminals were revealed by antisera to ACTH, gastrin, CCK, alpha-endorphin, beta-endorphin, gamma 1-MSH, insulin, motilin, human calcitonin, growth hormone, somatostatin, CRF, ovine prolactin and rat prolactin. Together with previously described results these findings demonstrate that at least 19 different peptidergic cell types are present in the Colorado potato beetle. Several of these cell types are identical with the known neurosecretory cells, while others have not been identified before. The functions of the immunoreactive neurons are as yet unclear, although in two cases the localization of these cells gives some clues. Thus the lateral neurosecretory cells, which are immunoreactive with antisera to beta-endorphin and ovine prolactin, may regulate corpus allatum activity, whereas a CRF immunoreactive substance seems to be used as neurotransmitter by antennal receptors. These immunocytochemical findings do not imply that the immunoreactive substances are evolutionarily related to the vertebrate peptides to which the antisera were raised. It is postulated that if the part of the substance recognized by a certain antiserum is functionally important for the insect, which should be so if the insect peptide is evolutionarily related to its vertebrate homologue, the antiserum should reveal homologous cells in different insect species. The consequence of this hypothesis is, that if an antiserum does not reveal homologous neurons in different insect species, the immunologically demonstrated substance is probably of little physiological importance, and will not be related evolutionarily to the vertebrate analogue. The positive immunocytochemical results in the Colorado potato beetle are discussed in relation to these considerations.
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PMID:Immunocytochemical localization of peptidergic neurons and neurosecretory cells in the neuro-endocrine system of the Colorado potato beetle with antisera to vertebrate regulatory peptides. 285 60

Previous studies indicated that gastrin-17 (G-17) and the octapeptide of colecystokinin (CCK-8) were equally potent in their interaction with receptors for 125I-[Leu15]G-17 on isolated canine parietal cells. These findings were inconsistent with the poor efficacy of CCK-8 compared with G-17 as stimuli of acid secretion in dogs. The present study examines the effects of G-17 and CCK-8 on the release of somatostatinlike immunoreactivity (SLI) from a fraction of small canine fundic mucosal cells separated by elutriation and placed in short-term culture. CCK-8 was considerably more potent and more effective than G-17 as a stimulant of SLI release from these cultured cells. CCK-8 was slightly more potent than G-17 in inhibiting 125I-[Leu15]G-17 binding to receptors in the same elutriator fraction. Our present findings support the hypothesis that the poor efficacy of CCK compared with G-17 as a stimulant of acid secretion may reflect pronounced activation of somatostatin-mediated acid-inhibitory mechanisms by CCK-8. The present data indicate that differences in affinity between CCK-8 and G-17 at the 125I[Leu15]G-17 receptor probably do not account for the greater efficacy of CCK-8; the receptor or cell activation mechanisms underlying this greater efficacy of CCK-8 on SLI release remain to be elucidated.
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PMID:Cholecystokinin potently releases somatostatin from canine fundic mucosal cells in short-term culture. 285 10

To determine the effect of vasoactive intestinal peptide (VIP) on the secretion of somatostatin by neurons, dispersed fetal cerebral cortical and diencephalic cells grown in culture were exposed on day 10 or 11 of culture to various concentrations of VIP, and for comparison to the structurally related peptides PHI (Peptide Histidine Isoleucine-27), growth hormone (GRH1-44-NH2) and secretin and to cholecystokinin. VIP elicited a dose-dependent release of somatostatin from both cortical and diencephalic cells, the lowest effective concentration being 6 X 10(-9) M. PHI also brought about release of somatostatin, but was between 0.06 and 0.1 times as potent as VIP. Placed together in a concentration of 10(-7) M, the two peptides did not have an additive effect. In this system GRH1-44-NH2, secretin and CCK octapeptide were without effect.
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PMID:Vasoactive intestinal peptide and PHI stimulate somatostatin release from rat cerebral cortical and diencephalic cells in dispersed cell culture. 286 Sep 51

The existence of an increasing number of peptides in both the gut and the brain provides the basis for the concept of a brain-gut axis. However, to date, no unifying hypothesis has been put forward to explain the physiologic significance of this remarkable phenomenon. The present study examines the central and peripheral actions on gastric function of cholecystokinin octapeptide (CCK-8), somatostatin, and bombesin, all of which exist in both the gut and brain. Intravenous infusion of CCK-8, in doses of 50, 100, and 200 pmol X kg-1 X hr-1, caused 28%, 38%, and 52% inhibition, respectively, of the rate of gastric emptying of a liquid meal in dogs. By contrast, the injection of 32, 64, and 128 pmol X kg-1 into the lateral cerebral ventricle of these dogs accelerated gastric emptying by 6%, 26%, and 32%, respectively. Bombesin, which stimulated gastric acid secretion in a dose-dependent manner but which had no effect on the submaximal acid response to pentagastrin when administered peripherally, inhibited in a dose-dependent manner the submaximal response to pentagastrin when given centrally, with a maximal inhibition of 66% +/- 5%, at a dose of bombesin of 180 pmol X kg-1. Similarly, somatostatin-14 caused graded inhibition of pentagastrin-stimulated acid secretion when it was administered peripherally but caused dose-dependent augmentation of the acid response when it was given centrally. Maximal inhibition of 51% of the pentagastrin response occurred with a peripheral dose of somatostatin of 800 pmol X kg-1 X hr-1. By contrast, maximal augmentation of the pentagastrin response of 78% occurred when a dose of 400 pmol X kg-1 of the peptide was injected into the lateral ventricle. We conclude that CCK-8, bombesin, and somatostatin have opposing actions on gastric function when administered centrally and peripherally. We propose that this phenomenon may be common to all neuropeptides of the brain-gut axis and may provide a basis for central regulation of gut function.
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PMID:Opposing central and peripheral actions of brain-gut peptides: a basis for regulation of gastric function. 286 11

A unique subset of interneurons which are rich in immunoreactive somatostatin (IRS) exists in the cerebral cortex. The regulation of IRS secretion by these cells is reviewed. Acetylcholine, glutamic acid and several neuropeptides including VIP, CCK, and metenkephalin have been identified as IRS secretagogues. The types of molecules which stimulate IRS release, the electrophysiologic effects of somatostatin, and the recognition of abnormal IRS levels in human CNS diseases were all used to formulate a working model of the role of the somatostatinergic cell in ongoing cerebral cortical function.
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PMID:Somatostatin and the cerebral cortex. 286 32

Gastrin-immunoreactive cells were fairly numerous in the pancreas and upper duodenum of the rat at about the time of birth. A minor population of these cells stained with antibodies directed against the N-terminal region of gastrin-34 as well as with antibodies directed against the C-terminal region. The remainder of the cells stained with the C-terminally directed antibodies only. Within a fortnight after birth all gastrin-immunoreactive cells disappeared from the pancreas and were greatly reduced in number in the duodenum; those that remained were probably CCK cells. Gastrin cells were rare in the antrum at birth and remained rare during the first days after birth. They increased in number, slowly until after weaning (15-20 days of age) and then more rapidly, until 25-30 days of age when the gastrin cell density reached that in adult rats. At the time of birth the gastrin concentration in serum was low; the subsequent increase during the first 2 weeks paralleled the development of the antral gastrin cell system. Adult postprandial serum gastrin concentrations were reached 12 days after birth. Somatostatin cells were rare in both the antral and oxyntic mucosa at birth. They increased gradually in number until about a month after birth when the cell density reached that seen in adult rats. In the oxyntic mucosa the ECL and A-like cells are the predominant endocrine (argyrophil) cell types. They were not detected until about 4 days after birth. Their number increased slowly until about 30 days of age. They did not stain argyrophil until about 2-4 weeks after birth. Parietal cells were few at birth; ultrastructurally they appeared to be in an active state and histochemically they were shown to contain carbonic anhydrase. The pH of the gastric content of newborn rats was close to 5; 15-17 days after birth the pH was about 4 in freely fed rats. In fasted rats shortly after birth the pH was about 4. Two weeks later it was around 2, which is the pH measured in older rats. Hence, the full capacity for acid secretion is probably not established until weaning. Fasting greatly lowers the serum gastrin concentration and the histidine decarboxylase activity of the ECL cells in adult rats. Before weaning, fasting produced these effects only to a minor degree.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Endocrine cells and parietal cells in the stomach of the developing rat. 286 80

Several secretagogues of exocrine pancreatic secretion have been proposed to act as regulators of pancreatic D-cell function. To characterize this relationship, we measured incremental responses of protein, bicarbonate, and circulating somatostatin to graded doses of intravenous cholecystokinin (CCK-33), CCK-8, caerulein, bombesin, secretin, and intraduodenally perfused HCl, sodium oleate, and L-phenylalanine in conscious dogs with gastric and pancreatic fistulas and compared them with postprandial values (to a beef meal). Bombesin produced dose-related increases in somatostatin secretion (maximal, 46% of meal response), but caerulein, CCK-33, and CCK-8 released only small amounts of somatostatin at doses equivalent for pancreatic protein secretion. Secretin did not stimulate somatostatin release at any dose studied, whereas intraduodenal HCl at a load submaximal for pancreatic bicarbonate secretion increased somatostatin levels slightly (maximal, 16% of meal response). L-Phenylalanine and sodium oleate markedly increased protein secretion, but only oleate clearly stimulated somatostatin release (maximal, 11% of meal response). Our results suggest a greater quantitative importance of the intestinal phase for exocrine pancreatic stimulation than for somatostatin release.
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PMID:Effect of exocrine pancreatic secretagogues on circulating somatostatin in dogs. 286 83

Protein- and fat-rich test meals elicit a strong stimulatory effect on postprandial somatostatin (SLI) and pancreatic polypeptide (PP) release, whereas carbohydrate-rich meals rather attenuate the response of both hormones. Since there is evidence that intestinal hormones might contribute to the postprandial SLI and PP response, it was the aim of the present study to determine in dogs the effect of low-dose cholecystokinin octapeptide (CCK-8) on basal hormone levels and also during a background infusion of amino acids or glucose. In a group of six conscious dogs, sulfated CCK-8 was infused intravenously (i.v.) via a hindleg vein at stepwise increasing infusion rates of 10, 30, and 50 pmol X kg-1 X h. The infusion of CCK was applied during a background infusion of saline (2 ml/min), glucose (0.2 g/min), or an amino acid mixture (8.5%, 2 ml/min). CCK-8 had no effect on plasma insulin and glucagon levels under all experimental conditions. Plasma SLI levels were significantly stimulated by all doses of CCK. This stimulatory effect was similar during background infusions of either saline, glucose, or amino acids, respectively. Pancreatic polypeptide (PP) levels rose 200-300 pg/ml during CCK plus saline. This was slightly attenuated by glucose. During CCK plus amino acids, the PP response was augmented to 600-800 pg/ml. Since secretin is also released after the ingestion of a meal and intraduodenal acidification is a potent stimulus not only of secretin but also of gastric and pancreatic SLI release, the effect of secretin was examined additionally.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulatory effect of glucose, amino acids, and secretin on CCK-8-induced somatostatin and pancreatic polypeptide release in dogs. 286 95


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