Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of intraperitoneally administered nitric oxide (NO) synthase inhibitors has been examined on the naloxone-precipitated withdrawal syndrome in morphine-dependent mice. L-NAME (30-200 mg/kg) and L-NOARG (7.5-50 mg/kg) induced a significant decrease of naloxone-precipitated withdrawal jumping and diarrhoea. However, L-NMMA (3.5-100 mg/kg), considered as a less potent NO synthase inhibitor, did not significantly affect the withdrawal signs in mice. Although a specificity of NO synthase inhibitors is not fully established, these results indicate that inhibition of NO synthesis in the central nervous system and periphery may significantly affect the morphine withdrawal phenomena. Accordingly, this study suggests an involvement of NO in morphine withdrawal syndrome.
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PMID:Inhibitory effect of nitric oxide (NO) synthase inhibitors on naloxone-precipitated withdrawal syndrome in morphine-dependent mice. 751 58

Bisacodyl and phenolphthalein are diphenylmethane laxatives that have effects on intestinal water and electrolyte transport and smooth muscle contractility. Nitric oxide (NO) is produced in the intestine, where it stimulates electrolyte secretion and relaxes smooth muscle. Therefore, we studied in rats the effect of these laxatives on diarrhea, fluid transport in vivo, gastrointestinal transit and NO synthase activity in the absence and presence of inhibitors of NO synthesis. Both laxatives (50 mg/kg p.o.) produced diarrhea, which was delayed in onset by 25 mg/kg (i.p.) of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). The L-NAME effect was reversed by the NO donor isosorbide-5-mononitrate (30-120 mg/kg i.p.). L-Arginine (600 and 1500 mg/kg i.p.) prevented the inhibitory effect of L-NAME on diarrhea. The laxatives evoked water and electrolyte secretion and enhanced the transit of a suspension of charcoal through the gastrointestinal tract. This was inhibited by L-NAME but not D-NAME. The inhibitor of inducible NO synthase, dexamethasone (0.03-0.3 mg/kg i.p.), prevented the effects of both laxatives on electrolyte and water transport. Stimulation by these drugs of NO synthase was also inhibited by dexamethasone. The results demonstrate that bisacodyl and phenolphthalein stimulate water and electrolyte secretion, promote transit of intraluminal contents and produce diarrhea in association with enhanced production of NO. Furthermore, it appears that the NO is derived principally from activation of an inducible form of NO synthase.
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PMID:Nitric oxide as a mediator of bisacodyl and phenolphthalein laxative action: induction of nitric oxide synthase. 752 56

1. Magnesium sulphate was studied for its effects on diarrhoea, fluid secretion, gastrointestinal transit and nitric oxide (NO) synthase activity in rats. 2. At a dose of 2 g kg-1 orally magnesium sulphate produced diarrhoea that was delayed in onset and intensity in a dose-related manner by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). This was prevented by the NO precursor, L-arginine and the NO donating compound, isosorbide-5-mononitrate (IMN). 3. Nitric oxide synthase activity was stimulated in gut tissue from rats given magnesium sulphate and this was inhibited by L-NAME. Dexamethasone (1 mg kg-1, i.p.), an inhibitor of inducible NO synthase, had no effect on magnesium sulphate-induced diarrhoea. 4. Magnesium sulphate stimulated fluid and electrolyte accumulation in the intestinal lumen; these effects were prevented by L-NAME but not D-NAME. 5. Gastrointestinal transit of a non-absorbable marker (charcoal suspension) was increased by oral magnesium sulphate from a mean value of 54.1% to 72.9% (P < 0.01), and this was prevented by pretreatment with L-NAME. 6. The results demonstrate that oral magnesium sulphate produces diarrhoea in rats by increasing the accumulation of fluid in the intestinal lumen and enhancing flow from the proximal to distal intestine. The mechanism involves release of NO, probably through stimulation of the constitutive form of NO synthase. Whether or not the effects of magnesium sulphate are due to an osmotic action or an intrinsic effect of the magnesium or sulphate ions cannot be determined from these experiments.
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PMID:Nitric oxide as a mediator of the laxative action of magnesium sulphate. 752 10

Previously, we demonstrated that two nonselective inhibitors of nitric oxide synthase (NOS), L-NG-nitroarginine (L-NNA) and L-NG-nitroarginine methyl ester (L-NAME), reduced some signs of morphine withdrawal in rats. The present work extended these studies to include 7-nitroindazole (7-NI), an inhibitor specific for cerebral NOS, and N(5)-(1-iminoethyl)-L-ornithine (L-NIO), a potent inhibitor of endothelial NOS. Behavioral effects of these four NOS inhibitors and clonidine, an alpha 2-adrenoceptor, agonist, on morphine withdrawal in rats were assessed. Rats received one 75-mg morphine pellet subcutaneously (SC). Three days later, NOS inhibitors were administered IP 1 h before withdrawal was precipitated with naloxone (0.5 mg/kg, SC) and scored. 7-NI, L-NIO, L-NAME and L-NNA produced dose-related decreases in weight loss, diarrhea, wet dog shakes and grooming. 7-NI also reduced mastication, salivation and genital effects. Clonidine produced effects similar to 7-NI. In awake, morphine-naive and morphine-dependent rats not subjected to withdrawal, 7-NI was the only NOS inhibitor that did not increase blood pressure. Because 7-NI attenuated more signs of opioid withdrawal than L-NNA, L-NAME or L-NIO without causing hypertension, 7-NI appears to warrant further testing as a potential candidate for human use.
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PMID:Comparison of 7-nitroindazole with other nitric oxide synthase inhibitors as attenuators of opioid withdrawal. 756 21

1. Castor oil (2 ml orally) produced copious diarrhoea in rats 3 h after its administration. 2. Pretreatment (intraperitoneal, i.p.) of rats with the NO synthesis inhibitors NG-nitro-L-arginine methyl ester (L-NAME, 1-25 mg kg-1) and NG-monomethyl-L-arginine (L-NMMA, 2.5-100 mg kg-1) inhibited or prevented castor-oil-induced diarrhoea. L-Arginine (150-600 mg kg-1, i.p.) administered to rats pretreated with L-NAME 10 mg kg-1, drastically reduced the antidiarrhoeal activity of L-NAME in a dose-related manner. D-Arginine (900 mg kg-1) did not modify the protection by L-NAME. 3. Pretreatment (i.p.) of rats with L-NAME (2.5-25 mg kg-1) decreased the intestinal fluid accumulation and Na+ secretion induced by castor oil. L-Arginine (600 mg kg-1) but not D-arginine (900 mg kg-1) counteracted the inhibitory effect of L-NAME (10 mg kg-1). 4. L-NAME (10 and 25 mg kg-1) had no significant effect on the intestinal transit in normal rats or those given castor oil. 5. These results provide evidence that nitric oxide (NO) could play an important role in castor-oil-induced diarrhoea.
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PMID:Inhibitors of nitric oxide synthetase prevent castor-oil-induced diarrhoea in the rat. 768 65

1. Castor oil (2 ml orally) produced diarrhoea in rats 1-7 h after challenge, which was associated with gross damage to the duodenal and jejunal mucosa. 2. The injury was accompanied by release of acid phosphatase into the gut lumen, indicating cellular injury. 3. Intraperitoneal injection of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 2.5-50 mg kg-1 twice), prevented the diarrhoea. The dose of L-NAME (50 mg kg-1) completely blocked the diarrhoea but increased the release of acid phosphatase and worsened the gross damage. 4. The NO donating compound, isosorbide-5-mononitrate (IMN, 150 mg kg-1 twice) reversed the effects of L-NAME (50 mg kg-1) on castor oil-induced diarrhoea, gross damage and acid phosphatase release. 5. The apparent dissociation of the diarrhoeal and intestinal mucosal damaging effects of castor oil suggest that NO has a protective effect on the rat duodenal and jejunal mucosa, but that NO mediates, in part, the diarrhoea effect of this laxative.
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PMID:Dissociation of castor oil-induced diarrhoea and intestinal mucosal injury in rat: effect of NG-nitro-L-arginine methyl ester. 788 64

The effect of NG-nitro-L-arginine methyl ester (L-NAME) on castor oil-induced diarrhea was studied in control rats and those treated with isosorbide dinitrate or isosorbide-5-mononitrate. Castor oil (2 ml) produced diarrhea that lasted at least 8 h. Pretreatment of the rats with L-NAME (1-25 mg/kg i.p.) 15 min before castor oil did not block the castor oil-induced diarrhea beyond 3 h after challenge but delayed its appearance (P < .05-.001). However, diarrhea was inhibited (P < .01-.001) during the entire 8 h if rats were treated twice with L-NAME (25 mg/kg) (15 min before and 3 h after castor oil). These findings suggest that L-NAME, once administered, loses its activity 3 h after its administration. The nitric oxide synthase substrate, L-arginine (150-600 mg/kg), reversed (P < .05-.01) the inhibitory effect of L-NAME on diarrhea induced by castor oil. This effect is enantiomer-specific because D-arginine (900 mg/kg) was without an effect. These results suggest that castor oil-induced diarrhea in rats involves the L-arginine nitric oxide pathway. This is further supported by the effect of isosorbide dinitrate (0.6-120 mg/kg) and isosorbide-5-mononitrate (0.6-120 mg/kg). When administered to castor oil-treated rats, these two nitric oxide-generating agents prevented in a dose-dependent fashion (P < .01-.001) the inhibitory effect of L-NAME (25 mg/kg).
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PMID:Nitric oxide and castor oil-induced diarrhea. 830 70

Senna (60 mg/kg orally) and cascara (800 mg/kg orally)-induced diarrhoea and net fluid secretion were studied in rats for a time period of 1-8 h. NG-Nitro-L-arginine methyl ester (L-NAME) (2.5-25 mg/kg i.p. twice, 15 min before and 4 h after laxative administration), an inhibitor of nitric oxide synthase, reduced the diarrhoeal response. This effect was counteracted by L-arginine (600 and 1500 mg/kg i.p. 15 min before laxative administration), the precursor of nitric oxide (NO). The senna- and cascara-stimulated fluid secretion was reduced by NG-nitro-L-arginine methyl ester 25 mg/kg i.p. (twice, 15 min before and 4 h after laxative administration), while the stereoisomer NG-nitro-D-arginine methyl ester (D-NAME) 25 mg/kg i.p. was without effect. These results suggest a possible involvement of NO in senna- and cascara-induced diarrhoea and fluid secretion.
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PMID:NG-nitro-L-arginine methyl ester reduces senna- and cascara-induced diarrhoea and fluid secretion in the rat. 877 57

The present study was undertaken to test the hypothesis that 5-HT stimulates nitric oxide (NO) generating neurons, and that these neurons participate in the mediation of 5-HT-induced fluid secretion. 5-HT induced electrogenic Cl- secretion in guinea-pig distal colon. This response was abolished by tetrodotoxin but not by atropine. The maximum response to 5-HT (10(-5) M) was inhibited by approximately 65% (P < 0.05, n = 6) by the NO synthase inhibitor, NG-nitro-L-arginine (L-NNA, 10(-4) M). The substrate of NO synthase, L-Arg (10(-3) M) reversed the inhibition of 5-HT-induced secretions by L-NNA. 5-HT-induced diarrhea in fasted mice was reduced by atropine in vivo. NG-Nitro-L-Arg methyl ester (L-NAME, 1-32 mg/kg, i.p.) dose-dependently inhibited 5-HT (1 mg/kg)-induced diarrhea. The inhibitory effect of L-NAME was reversed by L-Arg, but not D-Arg (600 mg/kg, i.p., respectively). Taken together, these data suggest that 5-HT-induced fluid secretion in the gut is partly due to the activation of neurons that generate NO.
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PMID:Is nitric oxide involved in 5-HT-induced fluid secretion in the gut? 878 22

The objective of this study was to determine the effects that certain nitric oxide synthase inhibitors have on the spontaneous intestinal and colonic inflammation that develops in HLA-B27 transgenic rats and compare these data to those obtained using sulfasalazine (SZ). In an attempt to more closely mimic the clinical situation, drug treatment was begun after the onset of colitis. HLA-B27 male rats that developed clinical signs of colitis (diarrhea/loose stools) at 17 wk of age were randomized into fours groups consisting of one untreated colitic group and three treatment groups that received either aminoguanidine (AG; 52 micromol/kg/day), NG-nitro-L-arginine methyl ester (L-NAME; 45 micromol/kg/day) or SZ (130 mg/kg/day) in their drinking water for 14 days. Aged-matched Fisher 344 male rats were used as healthy controls. After 3 wk of treatment, ileal and colonic mucosal permeabilities, granulocyte infiltration and nitric oxide were quantified using blood-to-lumen clearance of 51Cr-EDTA, tissue myeloperoxidase activity, and plasma levels of nitrate and nitrite, respectively. We found that both AG and L-NAME but not SZ significantly attenuated the increases in plasma nitrate and nitrite levels. Interestingly, all three drugs were effective at significantly attenuating the increases in myeloperoxidase activity in the distal colon. Treatment with AG and SZ but not L-NAME were effective at significantly attenuating the increase in ileal and colonic permeabilities. Quantitative histological analysis revealed that AG and L-NAME but not SZ significantly attenuated the increase in the mucosal thickness and crypt depth in the distal colon compared to untreated colitis. Taken together, these data demonstrate that oral administration of certain nitric oxide synthase inhibitors or SZ to animals with active colitis attenuates the colonic inflammation by at least two different mechanisms. One mechanism appears to be dependent on inhibition of NO production whereas the other mechanism does not.
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PMID:Effects of nitric oxide synthase inhibition or sulfasalazine on the spontaneous colitis observed in HLA-B27 transgenic rats. 945 20


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