nitroarginine and Diarrhea

Emodin is traditionally used as a laxative and is found to increase or decrease the contractility of intestinal smooth muscle in low doses and high doses, respectively. In this study, we propose that bidirectional regulation (BR) on the contractility of jejunal smooth muscle (CJSM) is inducible by emodin in the absence of control by the central nervous system. The results indicated that emodin-induced BR had the following characteristics. A stimulatory effect on CJSM was induced by emodin at 7 low contractile states, and an inhibitory effect was induced on CJSM at 7 high contractile states. Emodin-induced BR on myosin phosphorylation was also observed. BR was not observed in the presence of tetrodotoxin, suggesting that enteric nervous system is required for producing BR. The stimulatory effect of emodin on CJSM was abolished by atropine and diphenhydramine, respectively, suggesting that BR was correlated with cholinergic and histamine system while jejunal smooth muscle was at low contractile state. The inhibitory effect of emodin on CJSM was abolished by phentolamine, propranolol, and L-NG-nitroarginine (L-NNA), respectively, suggesting that BR was related to adrenergic hyperactivity and with a nitric oxide relaxing mechanism while jejunal smooth muscle was in a high contractile state. The exact mechanism, however, needs further investigation.

Topics: Animals; Atropine; Constipation; Diarrhea; Diphenhydramine; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Emodin; Enteric Nervous System; In Vitro Techniques; Jejunum; Laxatives; Muscle Contraction; Muscle, Smooth; Myosins; Nitroarginine; Phentolamine; Phosphorylation; Propranolol; Rats; Rats, Sprague-Dawley; Tetrodotoxin

Cisplatin treatment of rats results into a significant increase in the activity of Ca(2+)-independent nitric oxide synthase (NOS) in kidneys and liver. Significant enhancement of lipid peroxidation in gastric mucosa, kidneys and liver was also observed. The administration of NG-nitro-L-arginine methyl ester, an inhibitor of NOS, markedly reduced renal and gastrointestinal toxicity, and also decreased the content of blood urea nitrogen, serum creatinine, and incidence of diarrhoea along with a significant inhibition in lipid peroxidation in the target organs. The present report, while demonstrating the beneficial effect of the blockade of NO pathways during cisplatin chemotherapy, may be helpful in developing strategies for combating some of the toxic side-effects of the drug.

Topics: Animals; Blood Urea Nitrogen; Cisplatin; Creatinine; Diarrhea; Enzyme Inhibitors; Feeding Behavior; Gastric Mucosa; Kidney; Lipid Peroxidation; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Rats

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.

Topics: Animals; Body Fluids; Diarrhea; Digestive System; Digestive System Physiological Phenomena; Dose-Response Relationship, Drug; Enzyme Inhibitors; Guinea Pigs; In Vitro Techniques; Male; Mice; Mice, Inbred Strains; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Patch-Clamp Techniques; Rats; Serotonin; Serotonin Antagonists

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.

Topics: Amino Acid Oxidoreductases; Animals; Arginine; Behavior, Animal; Diarrhea; Male; Mice; Morphine Dependence; Naloxone; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; omega-N-Methylarginine; Substance Withdrawal Syndrome