Abstract

5-Hydroxytryptamine (5-HT) is an important neurotransmitter and hormone/paracrine agent mediating various enteric functions. Its precise physiological, pathological and pathophysiological role remains nuclear. Nitric Oxide (NO) is involved in the physiological modulation of peristalsis and intestinal transit by interacting with the part of neuronal mechanisms and affecting the gastrointestinal musculature. This study investigated the role of Nitric Oxide in 5-HT-induced intestinal motility and diarrhea. Intraperitoneal administration of 5-HT, produced a dose-related increase in the incidence of diarrhea in fasted mice. 5-HT (0.1 mg/kg i.p.) Induced diarrhea was inhibited by NG-Nitro-L-arginine ( L-NNA) (1-30 mg/kg) dose dependently. The Inhibitory effect of L-NNA was reversed by L-arginine (50-300 mg/kg i.p.) dose dependently but not by D-arginine (100 mg/kg i.p.). Subcutaneous administration of 5-HT (0.5-2.0 mg/kg) produced a dose-related increase in intestinal transit, 5-HT(1.0 mg/kg, s.c.) induced increased intestinal motility was not modified by L-NNA (1.0-40 mg/kg, i.p.) L-arginine (50-300 mg/kg i.p.) dose dependently Inhibited 5-HT-induced intestinal motility, which had been reversed by L-NNA (5-20 mg/kg, i.p.). L-NNA lnhibited the effect of L-arginine, without modifying the 5-HT-induced intestinal motility. These results provide evidence that nitric oxide may play a role in diarrhea, but not that of the 5-HT-induced intestinal motility in the rat in vivo.