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)

Duodenal fat such as oleate is known to influence gut functions by release of cholecystokinin (CCK), but the contribution of CCK endogenously released by duodenal fat or by diversion of pancreatic juice from the duodenum in the mechanism of mucosal integrity and gastroprotection has been little studied. This study was designed to compare the effect of CCK-8 and intraduodenal (i.d.) instillation of sodium oleate, or diversion of the pancreatic biliary secretions that are known to release CCK, on the gastric mucosal lesions induced by topical application of 100% ethanol or acidified aspirin (ASA) in rats with or without the pretreatment with a CCK-A receptor antagonist, loxiglumide, or with L-365,260 to block CCK-B receptors. In addition, the effect of suppression of prostaglandin (PG) biosynthesis by indomethacin (5 mg/kg i.p.), inhibition of nitric oxide (NO)-synthase by L-NAME (5 mg/kg i.v.), or blockade of sensory nerves by capsaicin (125 mg/kg s.c.) on the protective activity of sodium oleate was determined. Sodium oleate (50-200 mM i.d.), or diversion of pancreatic juice from the duodenum for 3 h that produced significant rise in plasma CCK levels, significantly reduced gastric lesions induced by 100% ethanol to an extent similar to that induced by exogenous CCK-8 (5 nmol/kg s.c.). The protective effect of oleate or diversion of pancreatic juice was accompanied by an increase in gastric blood flow (GBF). Both protection and accompanying hyperemia were completely abolished by blockade of CCK-A receptors with loxiglumide, whereas L-365,260, an antagonist of CCK-B receptors, had no effect. Oleate given i.d. significantly attenuated acidified ASA-induced gastric lesions and gastric secretion while increasing the luminal concentration of somatostatin. These effects were significantly reduced by loxiglumide but not by L-365,260. In contrast, CCK-8, which stimulated gastric acid secretion, failed to affect the lesions induced by acidified ASA and the decrease in the GBF produced by this ulcerogen. Indomethacin, which suppressed PG generation by approximately 90%, failed to influence the protective activity of oleate or CCK-8 against ethanol-induced lesions, whereas L-NAME, vagotomy, or sensory denervation significantly attenuated this protection and accompanying hyperemia. Addition to L-NAME of L-arginine, but not D-arginine, restored the protective and hyperemic effects of CCK-8 and duodenal oleate against gastric lesions induced by ethanol or acidified ASA. We conclude that endogenous CCK released by oleate or diversion of pancreatic secretion exerts a potent gastroprotective action on the stomach involving predominantly CCK-A receptors and depending on vagal activity, and hyperemia mediated by NO and sensory nerves but unrelated to acid secretory effects and endogenous PG.
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PMID:Involvement of endogenous cholecystokinin and somatostatin in gastroprotection induced by intraduodenal fat. 987 9

Carbon monoxide (CO) has been suggested as a novel messenger molecule in the brain. We now report on the cellular localization and hormone secretory function of a CO-producing constitutive heme oxygenase (HO-2) in mouse islets. Islet homogenates produced large amounts of CO which were suppressed dose-dependently by the HO inhibitor zincprotoporphyrin-IX (ZnPP-IX). We also show, for the first time, that glucose markedly stimulates the HO activity (CO production) in intact islets. A further potentiation was induced by the HO substrate hemin. Western blot showed that islet tissue expressed HO-2, and confocal microscopy revealed that HO-2 resided in insulin, glucagon, somatostatin, and pancreatic polypeptide cells. ZnPP-IX dose-dependently inhibited, whereas hemin enhanced, both insulin and glucagon secretion from glucose-stimulated islets. Stimulation or inhibition of CO production was accompanied by corresponding changes in islet cGMP levels. Exogenously applied CO stimulated insulin and glucagon release from isolated islets, whereas exogenous nitric oxide (NO) inhibited insulin and stimulated glucagon release. Islets stimulated by glucose or L-arginine displayed a marked increase in their NO-synthase (NOS) activity. Such an increase was suppressed by hemin, conceivably because NOS activity was inhibited by hemin-derived CO. Consequently, hemin enhanced L-arginine-induced insulin secretion. Insulin release stimulated by either hemin-derived CO or exogenous CO was strongly inhibited by the guanylate cyclase inhibitor ODQ, but it was unaffected by ZnPP-IX. Glucagon release induced by CO (but not by hemin) was inhibited by ODQ and partly inhibited by ZnPP-IX. We propose that the islets of Langerhans are equipped with a heme oxygenase-carbon monoxide pathway, which constitutes a novel regulatory system of physiological importance for the stimulation of insulin and glucagon release. This pathway is stimulated by glucose, is at least partly dependent on the cGMP system, and displays interaction with islet NOS activity.
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PMID:Heme oxygenase and carbon monoxide: regulatory roles in islet hormone release: a biochemical, immunohistochemical, and confocal microscopic study. 989 24

The occurrence and colocalization of several biologically active neuropeptides, catecholamine-, acetylcholine- or nitric oxide-synthesizing enzymes-tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (D beta H), choline acetyl-transferase (ChAT) and nitric oxide synthase (NOS I), respectively, as well as the vesicular acetylcholine transporter (VAChT) were investigated in the penile glans (GP), corpus and crura (CP), as well as in the retractor penis muscle (RPM) of juvenile and adult boars. Immunohistochemistry revealed that nerves immunoreactive (IR) to TH, D beta H, vasoactive intestinal polypeptide (VIP) and somatostatin (SOM) were the most numerous, followed (in decreasing order of density) by nerves IR to NOS, neuropeptide Y (NPY), substance P (SP), calcitonin gene-related peptide (CGRP), galanin (GAL), Leu5-enkephalin (LENK) and ChAT/VAChT. The CP contained the largest number of nerve fibres followed by the RPM, GP and corpus. Enzyme/peptide-containing nerves were associated with both the vascular and non-vascular penile structures. However, differences existed for their density and intrapenile distribution. Nerve terminals IR for different combinations of VIP, GAL or SOM were more frequent than those IR for NOS or CGRP in the non-vascular penile structures while the vasculature and the RPM received a prominent TH/D beta H-, VIP-, SOM- or NOS-IR nerve input. The present data indicate that the porcine penis receives nerve fibres that exhibit diverse chemical codes and that differences in the chemical coding of the nerve fibres may depend on their penile target-structure.
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PMID:Innervation of the fibro-elastic type of the penis: an immunohistochemical study in the male pig. 1009 43

In our previous studies we have shown that somatostatin and octreotide modulate the function of peritoneal macrophages and Kupffer cells in noncirrhotic livers. However, the effects of somatostatin on the Kupffer cells in cirrhotic livers are not known. In the present study, Kupffer cells, obtained from male rats with carbon tetrachloride-induced cirrhotic livers, were treated in vitro with somatostatin or octreotide and their effects on the release of nitric oxide, tumor necrosis factor-alpha (TNF-alpha) and peroxide (H2O2) determined. At concentrations of 10(-13) or 10(-10) to 10(-6) M of somatostatin or 10(-12) to 10(-10) M, or 10(-6) M of octreotide, the amount of nitric oxide released by Kupffer cells was significantly suppressed relative to that of untreated cells. Kupffer cells treated with less than 10(-12) M or greater than 10(-12) M of somatostatin or octreotide released less TNF-alpha compared to the untreated controls. In addition, zymosan-induced H2O2 release by Kupffer cells treated with 10(-9) to 10(-7) M somatostatin or with 10(-15) to 10(-13) M and 10(-9) to 10(-7) M of octreotide was greater than that of the untreated controls. These findings demonstrate that somatostatin and octreotide modulate the release of nitric oxide, TNF-alpha and H2O2 by Kupffer cells in cirrhotic livers depending on the concentrations of hormones used.
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PMID:Somatostatin and octreotide modulate the function of Kupffer cells in liver cirrhosis. 1010 Sep 24

We have examined the somatostatin-mediated modulation of acetylcholine release from intact chick embryo choroid tissue and compared these data with those obtained using acutely dissociated neuronal cell bodies from the chick ciliary ganglion. Acetylcholine release, evoked in a calcium-dependent manner by a high potassium (55 mM KCI) stimulation in both preparations, was inhibited almost completely by 100 nM somatostatin. Measurement of intracellular calcium in these neurons revealed that somatostatin blocked the large calcium transient that was observed in control neurons following KCI exposure. The modulatory effect of somatostatin on transmitter release was significantly attenuated by pre-treatment with pharmacologic agents that selectively block cyclic GMP (cGMP)-dependent protein kinase (PKG) or nitric oxide (NO) synthase. It is interesting that this prevention of somatostatin-mediated acetylcholine release inhibition occurred without reversal of the somatostatin-mediated block of the KCl-evoked calcium transient. Furthermore, a NO donor or cGMP analogue could block KCI-evoked acetylcholine release, but only cGMP could reduce the KCI-evoked calcium transient. Although cGMP could reduce the KCI-evoked calcium transient, a cGMP analogue was shown to reduce calcium ionophore-evoked transmitter release. Thus, somatostatin reduces acetylcholine release by modulating calcium influx, but the NO-PKG pathway can inhibit acetylcholine release, and alter somatostatin-mediated inhibition, by affecting transmitter release at some point after calcium entry.
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PMID:A nitric oxide/cyclic GMP-dependent protein kinase pathway alters transmitter release and inhibition by somatostatin at a site downstream of calcium entry. 1021 75

Nitric oxide (NO) and somatostatin (SS) are two important mediators of the exocrine and endocrine pancreas, exerting opposite effects on this organ. There is strong evidence suggesting an interaction between pancreatic NO and SS. The aim of this study was to determine whether L-arginine (L-Arg), the substrate for NO synthase (NOS), and Nomega-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, regulate pancreatic somatostatin-like immunoreactivity (SSLI) content and the SS mechanism of action in pancreatic acinar cell membranes. L-Arg (150 mg/kg, intraperitoneally (i.p.)), L-NAME (50 mg/kg, i.p.) or L-NAME plus L-Arg were injected twice daily at 8 h intervals for 8 days. L-Arg decreased pancreatic SSLI content as well as the number of SS receptors in pancreatic acinar cell membranes whereas L-NAME increased both parameters. The stable SS analogue SMS 201-995 induced a significantly lower inhibition of forskolin-stimulated adenylyl cyclase activity in pancreatic acinar cell membranes from L-Arg-treated rats whereas an increased inhibition was observed in pancreatic acinar membranes from L-NAME-treated rats. These results indicate that the NO system may contribute to the regulation of the pancreatic somatostatinergic system.
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PMID:Effect of nitric oxide on the somatostatinergic system in the rat exocrine pancreas. 1023 56

A subpopulation of cerebral cortical neurons constitutively express nitric oxide synthase (NOS) and, upon demand, produce a novel messenger molecule nitric oxide (NO) with a variety of proposed roles in the developing, adult, and diseased brain. With respect to the intensity of their histochemical (NADPH-diaphorase histochemistry) and immunocytochemical (nNOS and eNOS immunocytochemistry) staining, these nitrinergic neurons are generally divided in type I and type II cells. Type I cells are usually large, intensely stained interneurons, scattered throughout all cortical layers; they frequently co-express GABA, neuropeptide Y, and somatostatin, but rarely contain calcium-binding proteins. Type II cells are small and lightly to moderately stained, about 20-fold more numerous than type I cells, located exclusively in supragranular layers, and found almost exclusively in the primate and human brain. In the developing cerebral cortex, nitrinergic neurons are among the earliest differentiating neurons, mostly because the dominant population of prenatal nitrinergic neurons are specific fetal subplate and Cajal-Retzius cells, which are the earliest generated neurons of the cortical anlage. However, at least in the human brain, a subpopulation of principal (pyramidal) cortical neurons transiently express NOS proteins in a regionally specific manner. In fact, transient overexpression of NOS-activity is a well-documented phenomenon in the developing mammalian cerebral cortex, suggesting that nitric oxide plays a significant role in the establishment and refinement of the cortical synaptic circuitry. Nitrinergic neurons are also present in human fetal basal forebrain and basal ganglia from 15 weeks of gestation onwards, thus being among the first chemically differentiated neurons within these brain regions. Finally, a subpopulation of human dorsal pallidal neurons transiently express NADPH-diaphorase activity during midgestation.
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PMID:Nitrinergic neurons in the developing and adult human telencephalon: transient and permanent patterns of expression in comparison to other mammals. 1040 67

In the last decade, the knowledge of the pathogenesis of portal hypertension has increased dramatically. Indeed, apart from the well-known pathogenetic importance of structural factors, the role of vasoactive factors, which enhance the increase in intrahepatic resistance, has been highlighted. The two pathogenetic factors of portal hypertension are: the increase in portal outflow resistance and an increase in splanchnic blood flow, which worsens and maintains the increased pressure in the portal vein. The increase in portal inflow is part of the hyperdynamic circulatory syndrome, which is a haemodynamic characteristic of cirrhotic patients. In portal hypertensive patients, almost all the known vasoactive systems/substances are activated or increased and the most recent studies have stressed the importance of the endothelial factors, such as endothelins, nitric oxide and prostaglandins. Knowledge of the haemodynamic mechanisms allows a pathogenetic approach to the treatment of portal hypertension, particularly as far as medical therapy is concerned. The main categories of drugs used are: the vasoconstrictors (i.e., vasopressin, glypressin, somatostatin, non-selective beta-blockers), which act by decreasing portal inflow, and the vasodilators (i.e., nitroderivatives), which act mainly by decreasing intrahepatic portal resistance. Moreover, technological developments have introduced new tools for diagnosis, such as echo-colour-Doppler, and therapy, like variceal banding and transjugular intrahepatic porto-systemic shunt.
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PMID:Portal hypertension: state of the art. 1042 79

Nitric oxide (NO) exerts widespread and fundamental physiological effects. It is identical to the so-called endothelium-derived relaxing factor which regulates vascular tone. It has also been demonstrated to act as a neurotransmitter in both the peripheral and central nervous systems. NO is generated from L-arginine catalyzed by the NO synthases (NOS), of which two constitutive and one inducible form exist. NO stimulates the soluble guanylate cyclase which generates cyclic guanosine monophosphate (cGMP), that is believed to mediate the effects of NO. Recently, however, it has also been shown that NO is generated non-enzymatically from both L- and D-arginine by reaction with peroxide. The role of this pathway in the neuroregulation of growth hormone (GH) secretion has not yet been investigated. In rats, NO stimulates secretion of GH-releasing hormone (GHRH) and thus increases secretion of GH. However, it has also been observed that GHRH, in turn, increases production of NO in somatotroph cells, which subsequently blunts GH secretion. In humans, L-arginine stimulates pituitary GH release, but the mechanism is not fully clarified. Most studies suggest that an inhibition of somatostatin secretion is responsible for the effect. Infusion of low doses of the NOS inhibitor N(G)-nitro-L-arginine methyl ester have been shown not to change L-arginine-stimulated GH secretion. The effect of the NO donor molsidomine has also been found to have no influence on GH secretion. We investigated whether intravenous infusion of the NOS inhibitor N(G)-monomethyl-L-arginine (L-NMMA) influenced L-arginine-stimulated GH secretion in healthy young men. All subjects were examined twice in random order. On both occasions L-arginine was infused intravenously. This treatment was accompanied by either: L-NMMA co-infused or a saline infusion. Plasma cGMP was unchanged and identical in the two treatment groups, and the urine cGMP/creatinine ratio increased identically during both examinations. GH secretion increased significantly during L-arginine infusion and was not influenced by co-infusion of L-NMMA. There is so far no evidence that L-arginine stimulates GH release via NO production. However, it remains to be elucidated whether the doses of different L-arginine inhibitors/NO donors used in the previous studies were insufficient.
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PMID:The role of nitric oxide in L-arginine-stimulated growth hormone release. 1044 77

Gastrin is a hormone regulating gastric acid secretion and the growth of the gastrointestinal epithelium. It is expressed by endocrine tumors and by adenocarcinomas of the gastroenteropancreatic region and may represent an autocrine tumor growth factor. Gastrin is also implicated in the genesis of peptic ulcer disease both in conjunction with H. pylori infections and with gastrin-producing tumors. The secretion and expression of gastrin are under the paracrine control of somatostatin, produced by D cells situated in close contact with gastrin-producing G cells. D cells also contain neuronal nitric oxide synthase and appear to regulate apoptosis of G cells by paracrine release of nitric oxide. Both G and D cells are derived from a common multihormonal precursor cell present in the regenerative (isthmus) region of the gastric units. The precursor cells have been suggested to undergo asymmetrical divisions resulting in gastrin- and somatostatin-producing daughter cells that remain in paracrine contact during their migration into the glands. The precursor cells also give rise to the third main antropyloric endocrine cell type; the serotonin-producing EC cell. The maturation of all of these cell types is regulated by a number of transcription factors containing homeobox motifs (Pdx-1, Pax 4 and 6, Isl-1, Nkx6.1). Many of these also regulate the development of the central nervous system and the pancreas. The use of different combinations of these factors for regulating the expression of different hormones may explain the phenomenon of abberant hormone expression during development and carcinogenesis and the occurrence of multihormonal cells.
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PMID:Developmental biology of gastrin and somatostatin cells in the antropyloric mucosa of the stomach. 1070 44


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