UMLS:C0406810 - FACTA Search

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

To evaluate if L-arginine-nitric oxide-pathways are involved in the neural relaxation of the sphincter of Oddi, we studied the effect of nitric oxide synthase inhibition on electrical field stimulation-induced relaxation of the sphincter of Oddi in the guinea pig in vitro. After incubation with atropine (1 microM), phentolamine (1 microM) and propranolol (1 microM), histamine (50 microM) and cholecystokinin-octapeptide (25 nM) produced similar increases in sphincter tone. Subsequent field stimulation induced sphincteric relaxation, that was significantly greater when the initial tone had been raised by cholecystokinin (5 Hz, 59 +/- 9%; 10 Hz, 79 +/- 9%) compared to histamine (5 Hz, 27 +/- 3%; 10 Hz, 40 +/- 7%). N-omega-Nitro-L-arginine methyl ester (L-NAME, 100 microM), which competitively inhibits nitric oxide synthase, markedly suppressed this relaxation. The subsequent addition of L-arginine (1 mM), but not D-arginine (1 mM), restored the relaxation. Hexamethonium (100 microM) did not affect the relaxation, but tetrodotoxin (1 microM) completely abolished it. Sodium nitroprusside caused a dose-dependent relaxation of the sphincter (ED50 13 nM), which was unaffected by L-NAME. In conclusion, endogenous nitric oxide synthase products represent a major transmitter of non-adrenergic non-cholinergic relaxation of the sphincter of Oddi in the guinea pig. This relaxation is partially facilitated by cholecystokinin.
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PMID:Involvement of L-arginine-nitric oxide pathways in neural relaxation of the sphincter of Oddi. 768 81

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

In the present study we evaluated the effects of agents anticipated to change NO levels on the secretion of cholecystokinin (CCK) from STC-1 cells. After a 15-min treatment with the nitric oxide (NO) generating agent sodium nitroprusside (SNP; 10 microM), a 24% inhibition in basal CCK release and an increase in cellular guanosine 3',5'-cyclic monophosphate (cGMP) levels were noted. By contrast, SNP (10 microM) had no effect on CCK release stimulated by L-phenylalanine (20 mM). Inhibition of NO synthase (NOS) with NG-nitro-L-arginine methyl ester (L-NAME) produced dose-dependent stimulation in CCK release. L-NAME (100-400 microM) also inhibited ATP-sensitive potassium (KATP) channels in cell-attached patches. Pretreatment of cells with disopyramide (200 microM), a KATP channel blocker, blocked L-NAME stimulation of CCK release. After inhibition of potassium channel activity by L-NAME, addition of the nonhydrolyzable cGMP analogue 8-bromo-cGMP (1-2 mM) reactivated potassium channels. NO-generating agents had no effect on channel activity in inside-out membrane patches. It is concluded that NO may serve as an important regulator of basal CCK release.
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PMID:Regulation of cholecystokinin secretion in STC-1 cells by nitric oxide. 889 84

Caerulein, a non-selective agonist of cholecystokinin (CCK) receptors, is shown to suppress locomotor activity in rodents via stimulation of CCK(A) receptors. In the present study we examined the possible involvement of nitric oxide (NO) in caerulein-induced hypolocomotion in rats. Caerulein (10 microg/kg) markedly decreased the horizontal and vertical components of locomotor activity in rats measured in dark motility boxes. Pretreatment with a nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), at 5 mg/kg i.p., abolished the inhibiting action of caerulein on the horizontal activity, but did not affect the reduced frequency of rearing. The other doses of L-NAME (1, 10 and 20 mg/kg) were ineffective against caerulein. As L-NAME at this dose range does not stimulate locomotor activity, it is likely that NO is involved in the motor suppressant effect of systemically administered caerulein.
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PMID:Nitric oxide mediates caerulein-induced suppression of locomotor activity. 891 57

Nitric oxide (NO) production reportedly regulates guanosine 3', 5'-cyclic monophosphate (cGMP) formation and Ca2+ influx in pancreatic acini. We have investigated the functional roles of the NO/cGMP messenger system in rat pancreatic acini. In dispersed acini, the levels of amylase secretion, cytosolic [Ca2+]([Ca2+]i), NO synthase, and cGMP were measured. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 0.01-100 microM) had no effect on amylase secretion induced by various concentrations of carbachol, cholecystokinin octapeptide (CCK-8) or the high affinity CCK agonist, JMV-180. Similarly, L-NAME up to 100 microM did not affect the changes in Ca2+ spiking evoked by these secretagogues; nor was Ca2+ entry, refilling or oscillation altered by L-NAME. Sub- and supramaximal concentrations of these secretagogues did not change NO synthase activities compared with basal levels. While sodium nitroprusside (SNP), a NO donor, caused a 9.4-fold increase in cGMP levels compared with basal levels, carbachol, CCK-8 and JMV-180 had no effect. In addition, the guanylate cyclase inhibitor LY 83583 (10 nM to 10 microM) altered neither amylase secretion nor Ca2+ signaling induced by these secretagogues. These findings indicate that the stimulatory action of carbachol or CCK-8 is not mediated by NO or cGMP. To investigate whether cGMP stimulates pancreatic secretion we showed that both SNP and a cell-permeant cGMP analog at 0.1-1 mM stimulated amylase secretion and Ca2+ transients to a level equal to 10-15% and 13-24%, respectively, of those observed with maximal concentrations of secretagogues. The guanylate cyclase activator guanylin (1-10 microM), which increased cGMP levels 2.4-fold compared with basal levels, elicited a small amount of amylase secretion and a small Ca2+ transient. In conclusion, exogenous NO is capable of increasing endogenous cGMP, which results in a modest increase in the [Ca2+]i transient and pancreatic amylase secretion. However, the NO/cGMP system does not appear to be involved significantly in the mediation of Ca2+ signaling and amylase secretion stimulated by carbachol and CCK-8.
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PMID:Effect of uncoupling NO/cGMP pathways on carbachol- and CCK-stimulated Ca2+ entry and amylase secretion from the rat pancreas. 909 53

This study evaluates the hypothesis that cerulein relaxes the sphincter of Oddi (SO) via nitric oxide (NO). The spontaneous motility and the response to cerulein on the canine SO were recorded using a constant-perfusion technique. N(G)-L-arginine-methyl-ester (L-NAME) increased the spontaneous motility and dose-dependently reduced the cerulein-induced inhibitory response of the SO. After treatment with L-NAME at higher doses, cerulein induced an excitatory response. This effect was reversed by treatment with excess L-arginine. Similar results were obtained using cholecystokinin octapeptide in place of cerulein. In separate studies, cerulein generated increases in intracellular cAMP and cGMP levels in the SO. This indicates that the intracellular mechanism mediating cerulein-induced relaxation involves the production of cAMP and cGMP. On the other hand, treatment with L-NAME absorbed the increase in cAMP and cGMP levels by cerulein. These studies demonstrate that cerulein relaxes the canine SO mainly via NO, increasing intracellular cAMP and cGMP levels.
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PMID:Nitric oxide mediates cerulein-induced relaxation of canine sphincter of Oddi. 953 50

We studied whether non-adrenergic, non-cholinergic (NANC) relaxation of the rabbit sphincter of Oddi was influenced by tolerance to nitroglycerin (NG) in vitro. Sphincter of Oddi (SO) muscle rings precontracted with EC50 concentrations of cholecystokinin octapeptide (CCK8) were exposed to cumulative increases in NG concentrations and tested for relaxation by measurement of isometric tension. A separate group of six rings was subjected to a preceding exposure to 275 microM nitroglycerin over 60 min to induce in vitro tolerance to nitroglycerin. The rings (both tolerant and non-tolerant) were subjected to electrical field stimulation (FS: 50 V, 0.1 ms, 20 Hz, 3 and 10 stimuli). The rings were then preincubated with NANC solution: phentolamine, oxprenolol and atropine (all 1 microM) for 20 min and FS was applied again. FS was repeated after additional incubation with NG-nitro-L-arginine methyl ester (L-NAME), and inhibitor of NO synthase (30 microM) and after a successive incubation with 3 mM L-arginine (20 min). Maximum contractions produced by CCK8 in 'tolerant' and 'non-tolerant' sphincters were 29.9 +/- 5.8 and 28.3 +/- 5.2 mN, respectively. The sensitivity to CCK8 also was not different between the two groups with EC50 (-log M) values of 8.5 +/- 0.2 and 8.3 +/- 0.1, respectively. FS evoked twitchlike contraction followed by relaxation in the ampullary SO in both 'tolerant' and 'non-tolerant' preparations. Incubation in NANC solution resulted in monophasic relaxations in response to FS in non-tolerant sphincters but not in tolerant ones. L-NAME (30 microM) reversed NANC relaxation in non-tolerant muscle rings whereas it failed to modify NANC contractions in the tolerant preparations. L-arginine (3 mM) reversed the inhibitory effect of L-NAME on NANC relaxation in the 'non-tolerant' rings and it was without effect on FS-induced contractions in the 'tolerant' SO. As measured by radioimmunoassay, tolerance to NG was without any significant effect on tissue content of both cyclic adenosine 3':5' monophosphate (cAMP) and cyclic guanosine 3':5' monophosphate (cGMP). FS significantly increased tissue cAMP and cGMP content in 'non-tolerant' preparations. FS failed to increase the level of either cyclic nucleotide in 'tolerant' tissue. We conclude that NANC relaxation of the ampullary part of the rabbit SO is significantly impaired in the state of tolerance to NG 'in vitro'.
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PMID:Cross tolerance between nitroglycerin and neural relaxation of the rabbit sphincter of Oddi. 969 25

To examine whether and how local somatothermal stimulation inhibits the function of the sphincter of Oddi (SO) in humans and in animals with different types of SO, we measured the activity of SO in anesthetized cats and rabbits by using continuously perfused open-tip manometric methods. Local somatothermal stimulation was achieved by applying an electroheating rod 0.5 cm away from the skin area near the right subcostal region. A heating pad was applied to the corresponding area in patients undergoing endoscopic retrograde cholangiopancreatography and biliary manometry. The motility of the biliary tract in cats, in terms of gall bladder pressure, tonic and phasic contraction pressure and frequency of SO before and during local heat were significantly different, respectively. The local heat-induced SO relaxation was not inhibited by pretreatment with atropine, propranolol, phentolamine or anti-cholecystokinin-octapeptide, but was almost completely blocked by infiltration of local anesthetics. Pretreatment with a nitric oxide synthesis inhibitor also blocked the relaxation, which was reversed by pretreatment with L-arginine, but not by D-arginine. The inhibition of SO motility by local heat in rabbits was also blocked by pretreatment with L-NAME, and this blockade was reversed by L-arginine. Application of local heat on patients demonstrated obvious inhibitory SO responses. We conclude that local somatothermal stimulation inhibits the SO motility in animals with different types of SO through the activation of heat-sensitive neural release of nitric oxide. This procedure may represent a simplified approach for the treatment of diseases with hypofunction of the L-arginine/NO pathway.
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PMID:Local somatothermal stimulation inhibits the motility of sphincter of Oddi in cats, rabbits and humans through nitrergic neural release of nitric oxide. 971 66

In this study, we describe new methods for recording gastric emptying and in vivo measurements of intragastric pressure in fish. Using these methods, we investigated the effects of the sulphated octapeptide of cholecystokinin (CCK8) on gastric emptying and on stomach motility in vivo and in vitro. Gastric emptying of 99Tcm-labelled food was measured in swimming fish by using a gamma camera, counting consecutive 2.5 min periods for 18-42 h. After 20 h, 55.3+/-4.0 % of the labelled food remained in the stomach of the control fish (mean s.e.m., N=9). Vascular infusion of CCK8 (25 pmol kg-1 h-1) delayed gastric emptying so that 70.4+/-4.8 % of the labelled food remained in the stomach after 20 h (N=8). Gastric pressure changes in vivo were measured using a balloon surgically fitted into the cardiac or pyloric part of the stomach. In the cardiac part, intra-arterial infusion of CCK8 at 0.1 nmol kg-1 h-1 resulted in a decrease in the frequency and amplitude of rhythmic contractions, while higher doses started/increased contractions. Atropine blocked much of the basal contractile activity, but did not influence the CCK8-induced inhibition of contractile activity. The pyloric part of the stomach was unaffected by intra-arterial infusion of CCK8 or atropine. In vitro perfusion of the stomach (with a balloon placed in the cardiac part to record motility) with CCK8 at high concentrations (10(-7 )mol l-1 and above) augmented the spontaneous contractions, while lower concentrations had inconsistent effects. In addition, CCK8 (10(-7) to 10(-6 )mol l-1) decreased the amplitude of spontaneous contractions in longitudinal strip preparations, usually in combination with an increase in the resting tension. The decrease in amplitude was not affected by the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester hydrochloride (L-NAME; 10(-4 )mol l-1). Depending on the concentration and experimental arrangement, CCK8 had either inhibitory or excitatory effects on the cardiac stomach, suggesting the possible presence of different types of CCK receptor. We conclude that the predominant effect of CCK8 in vivo may be a slowing down of gastric emptying, presumably coinciding with a release of bile into the duodenum.
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PMID:Cholecystokinin affects gastric emptying and stomach motility in the rainbow trout Oncorhynchus mykiss. 985 5

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

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