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)

Adrenomedullin is a novel hypotensive adrenal polypeptide originally isolated from a human pheochromocytoma and is structurally related to calcitonin gene-related peptide and islet amyloid polypeptide. Using immunocytochemistry, the occurrence of adrenomedullin in the adrenal gland and gastro-entero-pancreatic region in the rat was examined and its effect on insulin secretion from isolated rat islets was determined. Adrenomedullin-like immunoreactivity occurred in noradrenaline- and adrenaline-producing cells in the adrenal gland. Gastrointestinal endocrine cells, with increased density distally, displayed adrenomedullin-like immunoreactivity; these cells constituted a subpopulation of the enterochromaffin (serotonin-containing) cells. Co-localization of adrenomedullin with somatostatin, glicentin, gastrin/cholecystokinin, peptide YY or islet amyloid polypeptide was not encountered. Adrenomedullin-immunoreactive cells were not observed in the pancreatic islets. At 1, 10 and 100 nmol/l, adrenomedullin stimulated insulin release from isolated rat islets in the presence of 3.3 mmol/l glucose (P < 0.05) and at 100 nmol/l, the peptide potentiated insulin secretion also in the presence of 8.3 mmol/l glucose (P < 0.05). These findings suggest that, besides being an adrenal hypotensive peptide, adrenomedullin may be a gut hormone with a potential insulinotropic function.
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PMID:Adrenomedullin: localization in the gastrointestinal tract and effects on insulin secretion. 879 72

1. The effect of a new type 2 selective somatostatin (SRIF) receptor antagonist (DC-41-33) on somatostatin-induced inhibition of pentagastrin-stimulated gastric acid secretion in conscious, chronic gastric fistula equipped rats was studied. 2. Infused intravenously, DC-41-33 dose-dependently inhibits SRIF-induced inhibition of pentagastrin-stimulated gastric acid secretion with an IC50 of 31.6+/-1.2 nmol kg(-1) versus 10 nmol kg(-1) SRIF and blocks the inhibitory effects of SRIF when simultaneously co-infused. Its effectiveness provides additional evidence that SRIF-inhibition of gastric acid release is a SRIF type 2 receptor-mediated process. 3. DC-41-33 is able to completely reverse the inhibitory effect of glucose-dependent insulinotropic polypeptides, GIP and GIP-(1-30)NH2, and glucagon-like polypeptide, GLP-1(7-36)NH2, on pentagastrin-stimulated gastric acid secretion thus confirming that they exert these effects through stimulation of endogenous SRIF release. 4. DC-41-33 only partially blocks potent amylin and adrenomedullin-induced inhibition of gastric acid secretion, therefore suggesting that somatostatin may not function as a primary mediator in the action of these peptides. 5. Our results indicate that DC-41-33, is a potent in vivo inhibitor of exogenous and endogenous SRIF in rats. It represents a new class of SRIF analogues which should eventually provide excellent tools for further evaluating the many physiological roles of SRIF and its five receptor subtypes.
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PMID:Examination of somatostatin involvement in the inhibitory action of GIP, GLP-1, amylin and adrenomedullin on gastric acid release using a new SRIF antagonist analogue. 984 48

This paper describes a 6-year-old Simmental bull with diabetes mellitus. The animal was referred to our clinic because of severe weight loss and chronic indigestion. Clinical examination revealed markedly disturbed general condition, impaired forestomach function and polyuria. There was aciduria, glucosuria and ketonuria. The most important biochemical findings were severe hyperglycemia, markedly increased activities of hepatic enzymes and severe metabolic acidosis. Plasma concentrations of insulin, insulin-like growth factor-I, thyroxine and 3,5,3'-triiodothyronine were lower than normal, whereas those of glucagon were higher than normal. Based on these findings, a diagnosis (secondary) diabetes mellitus was made. The bull was slaughtered and histological examination revealed mixed cell pancreatitis with severe degeneration of islet cells. Immunohistochemical examination of the pancreas showed that very few insulin-, glucagon-, somatostatin- and pancreatic polypeptide, insulin-like growth factor-I and adrenomedullin-producing islet cells were present.
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PMID:[Diabetes mellitus caused by pancreatitis in a bull]. 1123 31

Subcutaneous injections of adrenomedullin prevented reserpine-induced gastric mucosal damage in a dose-dependent manner (1-1000 ng/kg), but did not interfere with the lesions produced by ethanol administration. In pylorus-ligated rats adrenomedullin significantly reduced gastric volume, total and free acid output as well as ulcer formation. The gastroprotective activity of adrenomedullin was not present in rats pretreated with cysteamine. These results suggest that adrenomedullin exerts its antiulcer effect, when it is administered subcutaneously (s.c.), probably by a mechanism which involves somatostatin related transmission.
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PMID:Gastroprotective effect of adrenomedullin administered subcutaneously in the rat. 1212 44

alpha-Amidation is catalyzed by two enzymatic activities, peptidyl-glycine alpha-hydroxylating mono-oxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL), denoted collectively as peptidyl-glycine alpha-amidating mono-oxygenase (PAM), which also may include transmembrane and cytoplasmic domains. PAM is present in mammalian pancreas, where it appears to be abundant in the perinatal period. Nevertheless, there is no agreement on the cell type(s) that produces PAM or even on its presence in adults. In the present study we found PAM (PHM and cytoplasmic domain) immunoreactivity (IR) in A-, B-, and D-cells of adult mouse pancreas. In contrast to previous reports, PAM IR was found in B-cells of human and rat. Most of the B/D-cells were PAM immunoreactive, although with variable intensity, whereas less than half of A-cells displayed IR. Immunocytochemistry and Western blotting suggested the existence of different PAM molecules. Differences in the cellular distribution of IR for PAM domains were also observed. Whereas PHM-IR was extended throughout the cytoplasm in the three cell types, presumably in the secretory granules, IR for the cytoplasmic domain in A/D-cells was restricted to a juxtanuclear region, perhaps indicating its cleavage in Golgi areas. Although glucagon, insulin, and somatostatin are non-amidated, amidated peptides (glucagon-like peptide 1, adrenomedullin, proadrenomedullin N-terminal 20 peptide) were found in the three cell types.
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PMID:Immunocytochemical finding of the amidating enzymes in mouse pancreatic A-, B-, and D-cells: a comparison with human and rat. 1236 73

Adrenomedullin has recently been localized to enterochromaffin-like (ECL) and chief cells in the gastric fundus. It has been proposed that adrenomedullin may play a role in gastric mucosal defense and repair. In the present study, we have used the isolated, luminally perfused mouse stomach and superfused rat fundic segments to examine the effect of adrenomedullin on exocrine and endocrine secretion in this region of the stomach. Addition of adrenomedullin (1 pM to 1 microM) to the isolated mouse stomach caused a concentration-dependent decrease in acid secretion. The EC(50) value was 1.4 x 10(-9) and maximal inhibition of acid secretion was obtained at a concentration of 1 microM (31+/-4% below basal level, P<0.001). In rat fundic segments, superfusion with adrenomedullin (0.1 pM to 0.1 microM) caused a concentration-dependent increase in somatostatin secretion (EC(50), 1 x 10(-10)) that was accompanied by a reciprocal decrease in histamine secretion (EC(50), 1.2 x 10(-11)). Maximal stimulation of somatostatin secretion (60+/-5% above basal level, P<0.001) and inhibition of histamine secretion (50+/-5% below basal level, P<0.01) was obtained at a concentration of 0.1 microM. Changes in acid and histamine secretion induced by adrenomedullin reflected changes in somatostatin secretion and could be abolished by addition of somatostatin antibody. The axonal blocker, tetrodotoxin, also abolished the somatostatin and, consequently, the acid and histamine responses to adrenomedullin, implying that the effect of adrenomedullin on somatostatin secretion was mediated via activation of intramural neurons. We conclude that adrenomedullin, acting via intramural fundic neurons, stimulates somatostatin and thus inhibits histamine and acid secretion. This represents one mechanism by which adrenomedullin might enhance mucosal defense and repair.
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PMID:Adrenomedullin stimulates somatostatin and thus inhibits histamine and acid secretion in the fundus of the stomach. 1257 99

Intermedin (IMD), a novel member of the adrenomedullin (AM), calcitonin gene-related peptide (CGRP), amylin (AMY) peptide family, has been reported to act promiscuously at all the known receptors for these peptides. Like AM and CGRP, IMD acts in the circulation to decrease blood pressure and in the brain to inhibit food intake, effects that could be explained by activation of the known CGRP, AM, or AMY receptors. Because AM, CGRP, and AMY have been reported to affect hormone secretion from the anterior pituitary gland, we examined the effects of IMD on GH, ACTH, and prolactin secretion from dispersed anterior pituitary cells harvested from adult male rats. IMD, in log molar concentrations ranging from 1.0 pm to 100 nm, failed to significantly alter basal release of the three hormones. Similarly, IMD failed to significantly alter CRH-stimulated ACTH or TRH-stimulated prolactin secretion in vitro. However, IMD concentration-dependently inhibited GHRH-stimulated GH release from these cell cultures. The effects of IMD, although requiring higher concentrations, were as efficacious as those of somatostatin and, like somatostatin, may be mediated, at least in part, by decreasing cAMP accumulation. These actions of IMD were not shared by other members of the AM-CGRP-AMY family of peptides, suggesting the presence of a novel, unique IMD receptor in the anterior pituitary gland and a potential neuroendocrine action of IMD to interact with the hypothalamic mechanisms controlling growth and metabolism.
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PMID:Intermedin/Adrenomedullin-2 inhibits growth hormone release from cultured, primary anterior pituitary cells. 1626 57

Several circulating or urinary tumour markers can be used for the diagnosis and follow-up of functioning and clinically non-functioning neuroendocrine tumours of the pancreatic islet cells and intestinal tract. Among the specific tumour markers are serotonin and its metabolites--e.g. 5-hydroxyindoleacetic acid (5-HIAA)--in carcinoid tumours and the carcinoid syndrome, insulin and its precursors or breakdown products in insulinoma, and gastrin in gastrinoma. Plasma vasointestinal polypeptide (VIP) determinations have been used in the diagnosis of VIPoma, plasma glucagon for glucagonoma, and serum somatostatin for somatostatinoma. Among the tumour-non-specific markers are: chromogranins, neuron-specific enolase (NSE), alpha-subunits of the glycoprotein hormones, catecholamines, pancreatic polypeptide (PP), ghrelin and adrenomedullin.
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PMID:Biochemistry of neuroendocrine tumours. 1738 64

Angiogenesis, the process through which new blood vessels arise from preexisting ones, is regulated by several "classic" factors, among which the most studied are vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2). In recent years, investigations showed that, in addition to the classic factors, numerous endogenous peptides play a relevant regulatory role in angiogenesis. Such regulatory peptides, each of which exerts well-known specific biological activities, are present, along with their receptors, in the blood vessels and may take part in the control of the "angiogenic switch." An in vivo and in vitro proangiogenic effect has been demonstrated for erythropoietin, angiotensin II (ANG-II), endothelins (ETs), adrenomedullin (AM), proadrenomedullin N-terminal 20 peptide (PAMP), urotensin-II, leptin, adiponectin, resistin, neuropeptide-Y, vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), and substance P. There is evidence that the angiogenic action of some of these peptides is at least partly mediated by their stimulating effect on VEGF (ANG-II, ETs, PAMP, resistin, VIP and PACAP) and/or FGF-2 systems (PAMP and leptin). AM raises the expression of VEGF in endothelial cells, but VEGF blockade does not affect the proangiogenic action of AM. Other endogenous peptides have been reported to exert an in vivo and in vitro antiangiogenic action. These include somatostatin and natriuretic peptides, which suppress the VEGF system, and ghrelin, that antagonizes FGF-2 effects. Investigations on "nonclassic" regulators of angiogenesis could open new perspectives in the therapy of diseases coupled to dysregulation of angiogenesis.
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PMID:Nonclassic endogenous novel [corrected] regulators of angiogenesis. 1754 Sep 6

The aim of the present study is to provide a review of the expression and action of trophic factors in the carotid body. In glomic type I cells, the following factors have been identified: brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, artemin, ciliary neurotrophic factor, insulin-like growth factors-I and -II, basic fibroblast growth factor, epidermal growth factor, transforming growth factor-alpha and -beta1, interleukin-1beta and -6, tumour necrosis factor-alpha, vascular endothelial growth factor, and endothelin-1 (ET-1). Growth factor receptors in the above cells include p75LNGFR, TrkA, TrkB, RET, GDNF family receptors alpha1-3, gp130, IL-6Ralpha, EGFR, FGFR1, IL1-RI, TNF-RI, VEGFR-1 and -2, ETA and ETB receptors, and PDGFR-alpha. Differential local expression of growth factors and corresponding receptors plays a role in pre- and postnatal development of the carotid body. Their local actions contribute toward producing the morphologic and molecular changes associated with chronic hypoxia and/or hypertension, such as cellular hyperplasia, extracellular matrix expansion, changes in channel densities, and neurotransmitter patterns. Neurotrophic factor production is also considered to play a key role in the therapeutic effects of intracerebral carotid body grafts in Parkinson's disease. Future research should also focus on trophic actions on carotid body type I cells by peptide neuromodulators, which are known to be present in the carotid body and to show trophic effects on other cell populations, that is, angiotensin II, adrenomedullin, bombesin, calcitonin, calcitonin gene-related peptide, cholecystokinin, erythropoietin, galanin, opioids, pituitary adenylate cyclase-activating polypeptide, atrial natriuretic peptide, somatostatin, tachykinins, neuropeptide Y, neurotensin, and vasoactive intestinal peptide.
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PMID:Trophic factors in the carotid body. 1877 56


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