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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the isolated rat pancreas the effect of intrapancreatic non-adrenergic non-cholinergic nerves was examined upon insulin, glucagon and somatostatin release during perturbations of perfusate glucose. Elevation of glucose from 1.6 to 8.3 mmol/l increased insulin and somatostatin secretion and inhibited glucagon release. The first phase of insulin secretion was significantly reduced by the neurotoxin tetrodotoxin to 55% of the controls (p < 0.05). The somatostatin response was attenuated by tetrodotoxin while the change of glucagon remained unaffected. In contrast the combined adrenergic and cholinergic blockade with atropine, phentolamine and propranolol (10(-5) mol/l) did not modify the insulin, glucagon and somatostatin response. When glucose was changed from 8.3 to 1.6 mmol/l, the reduction of insulin and somatostatin release was not modified by tetrodotoxin, but stimulation of glucagon was significantly attenuated by 60-70% (p < 0.03), which was similar to the effect of combined adrenergic and cholinergic blockade. Subsequently, the effect of neural blockade was examined during more physiological perturbations of perfusate glucose levels. When glucose was changed from 3.9 to 7.2 mmol/l, tetrodotoxin also attenuated first phase insulin response by 40% while cholinergic and adrenergic blockade had no effect. The nitric oxide synthase inhibitor NG-Nitro-L-arginine-methyl-ester (L-NAME) did not alter the glucose-induced insulin response indicating that nitric oxide is not involved in this mechanism. It is concluded that neural non-adrenergic non-cholinergic mechanisms contribute to the first, but not second phase of glucose-induced insulin release. Non-adrenergic non-cholinergic effects do not participate in regulation of glucagon and somatostatin secretion under the conditions employed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Contribution of neural intrapancreatic non-cholinergic non-adrenergic mechanisms to glucose-induced insulin release in the isolated rat pancreas. 147 64

This study set out to identify the neurotransmitters involved in autonomic vasodilatation of the guinea pig uterine artery. Non-noradrenergic, paracervical neurons supplying this artery contain at least four neuropeptides: vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), dynorphin A (1-17) and somatostatin, probably in addition to acetylcholine. Transmural nerve stimulation of arterial segments precontracted with phenylephrine (3 x 10(-7) mol l-1 and treated with guanethidine (10(-6) mol l-1), produced relaxations which varied in form with the frequency of stimulation and the length of the pulse train. The relaxations were monophasic at low frequencies (< 2 Hz), and were biphasic at higher frequencies (> 5 Hz) and with longer pulse trains (> 50 pulses). Neither phase of the relaxations was reduced by hyoscine (10(-6) mol l-1), or by removal of the endothelium. The faster phase of the relaxations was selectively reduced (by 61%) during treatment with L-nitro-arginine methyl ester (L-NAME; up to 3 x 10(-5) mol l-1). This reduction was reversed by an excess of L-arginine, indicating that the fast relaxation was mediated by nitric oxide, possibly acting as a neurotransmitter. The slower phase of the neurogenic relaxation was preferentially reduced (by 43%) by the endopeptidase, trypsin (1-3 micrograms.ml-1). As VIP is the only currently identified peptide present in the paracervical neurons which causes vasodilatation, it is likely that VIP, or a closely-related peptide, is the transmitter responsible for the slow relaxation. Acetylcholine and an opioid peptide also seem to be released from the vasodilator neurons, but their effects were small, and may have been restricted to pre-synaptic sites. The slower neurogenic relaxations were inhibited by exogenous neuropeptide Y (68% reduction in amplitude), and were slightly potentiated by somatostatin (21% increase in amplitude). Therefore, endogenous stores of these peptides may also contribute to the sum effect of stimulating the paracervical vasodilator neurons. In conclusion, many different substances may act as autonomic co-transmitters from these pelvic vasodilator neurons.
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PMID:Co-transmission from autonomic vasodilator neurons supplying the guinea pig uterine artery. 809 24

The signal transduction cascade between the activation of the somatostatin (SOM) receptor and modulation of transmitter release was study using Acetylcholine (Ach) release measurements and patch clamp recordings of Ca2+ current from acutely dissociated St 40 ciliary ganglion neurons. As in intact synapses, somal ACh release was blocked by 100 nM SOM or 100 microM dibutyril cGMP, and the SOM-mediated inhibition could be reversed by 10 microM 1-NAME (a selective inhibitor of nitric oxide synthase, NOS) or 100 microM Rp-8p-CPT-cGMPs (a selective inhibitor of a cGMP protein dependent kinase, PKG). In whole cell recordings, SOM inhibition of Ca2+ current rapidly relaxes to control levels but is sustained in perforated patch recordings which decreases cell dialysis. Inhibition of NOS or PKG in perforated patch recordings, however caused SOM effects to become transient again. We hypothesize that PKG alters the characteristics of the membrane-delimited G protein inhibition of Ca2+ current. Therefore SOM receptors trigger a membrane-delimited signal transduction cascade that is modulated by soluble messengers, converging on voltage activated Ca2+ channels. When both pathways are active together, SOM causes a sustained inhibition of neuronal Ca2+ current leading to a decrease in transmitter release.
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PMID:Membrane delimited and intracellular soluble pathways in the somatostatin modulation of ACh release. 863 27

1. A possible interaction between cyclic AMP and nitric oxide (NO) in mediating the relaxant effect of vasoactive intestinal polypeptide (VIP) on intestinal smooth muscle cells has been investigated. The effects of the inhibitor of NO synthesis, NG-nitro-L-arginine methyl ester (L-NAME), have been studied on VIP-, forskolin-, and 8 bromo-cyclic AMP- induced relaxation of cells, dispersed by enzymatic digestion of muscle strips from the circular layer of guinea-pig ileum. 2. VIP alone did not modify the length of isolated muscle cells. By contrast, when the cells were contracted by cholecystokinin octapeptide, CCK8 (10 nM), VIP inhibited this contraction, inducing a concentration-dependent relaxation of the cells. Maximal relaxation was induced by 1 microM VIP (EC50 = 408.2 +/- 16.7 pM). 3. N-ethylmaleimide, inhibitors of adenylate cyclase or somatostatin, abolished the relaxing effect of VIP. (R)-p-cAMPs, an antagonist of cyclic AMP on protein kinase A also inhibited the VIP-induced relaxation by 92.1 +/- 6.3%. Inhibitors of nitric oxide synthase (NOS), L-NAME and L-NMMA, partially inhibited VIP-induced relaxation. The effect of L-NAME was reversed by L-arginine but not by D-arginine. 4. (R)-p-cAMPS and L-NAME also inhibited the cell relaxation induced either by forskolin which directly stimulates adenylate cyclase activity or 8-bromo-cyclic AMP, an analogue of cyclic AMP. 5. When cells were incubated for 30 min with dexamethasone 10 microM, a glucocorticoid known to decrease the synthesis of iNOS, the relaxing effect of a maximal concentration of VIP was decreased by 52 +/- 4% and L-NMMA had no further effect on this residual VIP-induced relaxation. Milrinone, a phosphodiesterase type III inhibitor, potentiated the relaxant effect of VIP. 6. These data demonstrate that the intracellular pathway mediating the relaxant effect of VIP in intestinal smooth muscle cells includes the sequential activation of adenylate cyclase, protein kinase A, activation of NOS and finally production of NO and cyclic GMP. NO could in turn regulate the cyclic AMP-dependent pathway of cell relaxation.
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PMID:VIP-induced relaxation of guinea-pig intestinal smooth muscle cells: sequential involvement of cyclic AMP and nitric oxide. 876 68

The physiological or pharmacological role of glucagon in the postprandial regulation of gastrointestinal motility has not yet been clarified. To clarify it, the following experiments were performed on conscious dogs. Antral, duodenal, jejunal and ileal contractile activities were monitored by chronically implanted strain gauge force transducers without restraint. The serum gastrin concentration in response to ingestion was measured by radioimmunoassay. 1) When glucagon (5 approximately 50 microg/kg, drip infusion for 5 minutes) was administered before ingestion of meal or 2 hours after ingestion, it inhibited postprandial motility dose-dependently in the antrum, while enhancing it in the duodenum, jejunum and ileum. 2) At the same time, glucagon inhibited the meal induced elevation of the serum gastrin concentration. 3) On the other hand, glucagon did not inhibit the contractions induced by pentagastrin (4 microg/kg,s.c.) or those induced by acetylcholine chloride (0.5 mg/kg, drip infusion for 10 minutes) in any region. 4) These glucagon-induced inhibitory effects in postprandial antral motility were not affected by phentolamine (0.5 mg/kg, i.v.) or nitro-L-arginine-methyl ester (L-NAME) (3 mg/kg/hr, drip infusion for 30 minutes). These results suggest that: 1) Glucagon inhibits the postprandial elevation of the serum gastrin concentration and thus inhibits postprandial antral motility. 2) On the other hand, in the intestine, glucagon-induced inhibitory responses might be reversed by glucagon-induced excitatory responses through preganglionic cholinergic motor neurons. 3) The mechanism of inhibition of gastrin release was not definite in my experiments, but one of the candidates may be activation of somatostatin release from the D cells by glucagon.
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PMID:Pharmacological regulation of postprandial gastrointestinal motility by glucagon in conscious dogs. 963 22

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

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

The turnover of the epithelium of the gastrointestinal tract is regulated by a balance between cell multiplication and cell loss. We examined the effects of starvation on apoptosis in endocrine and other epithelial cells of rat antropyloric mucosa. Apoptosis was determined by the TUNEL reaction combined with immunocytochemical staining for gastrin and somatostatin. Apoptotic cell morphology was determined by bisbenzimide staining for DNA. Both gastrin and somatostatin cells showed a significantly lower apoptotic index than the general epithelium. This agrees with the longer turnover kinetics of gastric endocrine cells. On starvation, the apoptotic index of the general epithelium and of the gastrin but not of the somatostatin, cells increased significantly. This was prevented by the nitric oxide synthase (NOS) inhibitor L-NAME but not by its inactive stereoisomer D-NAME. Immunoreactive neuronal NOS was present in somatostatin cells, in nonendocrine cells predominating in the surface and pit epithelium, and in rare nerve fibers. Endothelial cell NOS was present in vessels, whereas the inducible isoform was barely detectable. Thus, endogenous NOS isoforms participate in regulating antropyloric epithelial apoptosis during starvation. The close paracrine relation between somatostatin cells and gastrin cells suggests that the former regulates apoptosis of the latter through release of NO.
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PMID:Apoptosis in rat gastric antrum: evidence that regulation by food intake depends on nitric oxide synthase. 1065 93

Nitric oxide (NO) is a highly reactive gas that has been suggested to function as a neurotransmitter in the neuroendocrine system. In this work, we have evaluated the role of NO pathways in growth hormone (GH) secretion by assessing the effect of L-arginine infusion, a precursor of NO formation, and L-NAME, a nitric oxide synthase (NOS) inhibitor. The experiments were carried out on 7 adult beagle dogs. A saline infusion was carried out on all the dogs as a control test. L-arginine (infusion i.v. 10 g in 100 ml of saline, from t = 0 to 30 min) and L-nitro-arginine-methyl ester, L-NAME (infusion of 300 microg/kg in 120 ml of saline, from t = -30 to 45 min) were administered alone and together with growth hormone-releasing hormone (GHRH) (i.v. bolus at 0 min, at a dose of 100 microg), the synthetic GH secretagogue GHRP-6 (i.v. bolus at 0 min, at a dose of 90 microg), and the 5-HT1D serotonin receptor agonist sumatriptan, SUM (s.c. injection at the dose of 3 mg). Plasma cGH was determined by RIA. Results were evaluated by one-way analysis of variance, followed by the Newman-Keuls test for multiple comparisons. L-arginine administration resulted in a slight increase in plasma cGH in comparison with saline controls. Combined administration of L-arginine and GHRH enhanced cGH release in comparison with GHRH alone. L-NAME alone did not modify baseline cGH levels, but completely suppressed the GH release induced by GHRH or GHRP-6. It also strongly reduced, but did not abolish the effect of the two peptides (GHRH plus GHRP-6) administered together. Finally, administration of the 5-HT1D agonist SUM induced a significant cGH secretion in all dogs, a response which was not modified when L-NAME was administered in combination with SUM. In conclusion, our data show that inhibition of NO blunts both GHRH or GHRP-6-induced cGH release, and are compatible with the hypothesis that it acts by decreasing hypothalamic somatostatin release.
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PMID:Involvement of nitric oxide in the regulation of growth hormone secretion in dogs. 1159 77

Using altitude hypoxia model, in situ hybridization and NADPH-d histochemistry, we investigated the effects of ketamine and L-NAME (blocker of NOS) on NOS and somatostatin mRNA (SS mRNA) expression in the rat hypothalamus following acute altitude hypoxia. It was revealed that acute altitude hypoxia induced NOS and SS mRNA overexpression in the rat hypothalamus. When pretreated with NMDA receptor antagonist ketamine and L-NAME, NOS and SS mRNA expression were inhibited significantly. These results suggest that NMDA receptor activation participates in the expression of NOS and SS mRNA in the rat hypothalamus subjected to acute altitude hypoxia. Meanwhile, hypothalamic endogenous NO may mediate expression of SS mRNA.
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PMID:[Ketamine and L-NAME inhibit NOS and somatostatin mRNA expression induced by altitude hypoxia in the rat hypothalamus]. 1196 80


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