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)

Chronic hypoxic pulmonary hypertension (PH), associated with increased pulmonary arterial pressure (PPA) and right ventricular hypertrophy (RVH), correlates significantly with calcitonin gene-related peptide (CGRP) and somatostatin (SOM) levels in lung and blood. CGRP's role in regulation of PPA in chronic hypoxia and its potential interactions with SOM were investigated. CGRP, its antibody (ab) and blocker, CGRP-(8-37), SOM-14, SOM-28, and SOM-ab, respectively, were infused into the pulmonary circulation of hypobaric hypoxia rats for 4, 8, and 16 days. Thereafter, under pentobarbital sodium anesthesia, PPA was measured in the right ventricle and main pulmonary artery. Chronic CGRP infusion prevented PH at all times, whereas immunoneutralization and receptor blocking exacerbated PH. SOM-28 also exacerbated while SOM-14 and SOM-ab decreased PH. RVH generally reflected the PPA. Radioimmunoassay confirmed successful infusion of the peptides with negligible peptide degradation in the pumps throughout 16 days and showed complete immunoneutralization of CGRP with its ab. Peptide levels in lung tissue suggest inhibition of CGRP release by SOM-28 and increased plasma SOM with CGRP infusion. In vitro pharmacological studies suggest that CGRP exerts a receptor-mediated nonadrenergic, nonmuscarinic vasodilatory effect in the lung which is independent of endothelium-derived relaxing factor and does not involve ATP-dependent potassium channels. We conclude that endogenous CGRP plays an important role in pulmonary pressure homeostasis during hypoxia, by directly dilating pulmonary vasculature, thus ameliorating the development of chronic hypoxic pulmonary hypertension in rats.
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PMID:CGRP and somatostatin modulate chronic hypoxic pulmonary hypertension. 135 80

We have previously shown that the somatostatin (SRIF) sst2 receptor-selective peptide, BIM-23027, is a potent antisecretory agent in rat isolated distal colonic mucosa (RDCM) and in radioligand binding studies in RDCM membranes, it only maximally inhibited approximately 40% of [125I]-Tyr11-SRIF-14 binding (McKeen ES, Feniuk W, Humphrey PPA (1995) Naunyn-Schmiedeberg's Arch Pharmacol 352:402-411). The aim of this study was to characterise the BIM-23027-sensitive and -insensitive SRIF binding sites in more detail and to compare their properties with those of the recombinant sst2 receptor stably expressed in mouse fibroblast (Ltk-) cells. SRIF-14, SRIF-28, CGP-23996 and D Trp8-SRIF-14 abolished [125I]-Tyr11-SRIF-14 binding (pIC50 values, 8.7-9.7) but the competition curves had Hill slopes which were less than unity. Octreotide and L-362,855 inhibited binding over a wide concentration range (0.1 nM-1 microM) and inhibition of binding was incomplete at the highest concentration studied. BIM-23056 (pIC50 < 6.5) was a weak inhibitor of [125]-Tyr11-SRIF-14 binding. GTP gamma S decreased [125I]-Tyr11-SRIF-14 binding by 40%. Further binding experiments with [125I]-Tyr11-SRIF-14 were carried out in RDCM in the continuous presence of BIM-23027 (1 microM). Under these conditions, seglitide had no effect on [125I]-Tyr11-SRIF-14 binding at concentrations up to 10 microM, whilst SRIF-14 and SRIF-28 abolished specific [125I]-Tyr11-SRIF-14 binding in a manner which was consistent with the ligand binding to two sites. SRIF-14 and SRIF-28 displayed high affinity (pIC50 values of 7.8 and 7.3) for the remaining sites. Octreotide, L-362,855 and BIM-23056 were weak inhibitors of [125I]-Tyr11-SRIF-14 binding (pIC50 < 6.5). [125I]-BIM-23027 labelled a single population of SRIF binding sites in RDCM membranes and mouse fibroblast (Ltk-) cells stably expressing the human recombinant sst2 receptor. There was a significant correlation between the affinity estimates of a range of SRIF analogues at inhibiting [125I]-BIM-23027 binding in RDCM membranes and binding to the recombinant sst2 receptor in Ltk- cells, suggesting that the sites labelled by [125I]-BIM-23027 in RDCM are similar to the sst2 receptor. GTP gamma S (100 microM) decreased [125I]-BIM-23027 binding in RDCM by 60%. The results from these studies demonstrate that [125I]-Tyr11-SRIF-14 labels a heterogeneous population of high affinity SRIF binding sites in RDCM membranes. The majority of these sites are insensitive to GTP gamma S and display negligible affinity for the cyclic hexapeptides, BIM-23027 and seglitide. The remaining high affinity binding sites can be selectively labelled with [125I]-BIM-23027, are sensitive to GTP gamma S and show similar characteristics to the recombinant sst2 receptor which appears to mediate the antisecretory effects of SRIF in the mucosa (McKeen ES, Feniuk W, Humphrey PPA (1995) Naunyn-Schmiedeberg's Arch Pharmacol 352:402-411).
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PMID:Identification and characterisation of heterogeneous somatostatin binding sites in rat distal colonic mucosa. 893 50

In the present study, we investigated types of pancreatic endocrine cells and its respective peptides in the Brazilian sparrow species using immunocytochemistry. The use of polyclonal specific antisera for somatostatin, glucagon, avian pancreatic polypeptide (APP), YY polypeptide (PYY) and insulin, revealed a diversified distribution in the pancreas. All these types of immunoreactive cells were observed in the pancreas with different amounts. Insulin-Immunoreactive cells to (B cells) were most numerous, preferably occupying the central place in the pancreatic islets. Somatostatin, PPA, PYY and glucagon immunoreactive cells occurred in a lower frequency in the periphery of pancreatic islets.
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PMID:Immunocytochemical study of the distribuition of endocrine cells in the pancreas of the Brazilian sparrow species Zonotrichia Capensis Subtorquata (Swaison, 1837). 1827 28