Nitric oxide is a neurotransmitter in the chloride secretory response to serotonin in rat colon

Background. Serotonin (T-hydroxytryptamine [5-HT]) has been shown to induce chloride secretion through a nonadrenergic/noncholinergic neural pathway, mediated by a 5-HT3 receptor We hypothesized that 5-HT3-induced Cl- secreti on is ultimately mediated by nitric oxide (NO). Methods. Unstripped sheets of rat distal colon were mounted in Ussing chamb ers and short-circuited. The 5-HT3 receptor agonist, 2-methyl-5-HT, was add ed in the absence and presence of the NO synthase inhibitor; L-NAME. Compan ion studies involved the addition of sodium nitroprusside to tissue that wa s incubated with or without tetrodotoxin Results. L-NAME caused a significant reduction in the 2-methyl-5-HT-induced change in circuit current, in a concentration-dependent manner Sodium nitr oprusside caused a change in, circuit current over baseline in 5 minutes. T he addition of tetrodotoxin did not significantly alter the change in circu it current; however the apical Cl- channel blocker anthracene-9-carboxylic acid, abolished this response. Conclusions. Neurally mediated Cl- secretion in response to 2-methyl-5-HT i s inhibited by an NO synthase inhibitor Exogenous NO mimics this response, which is unaffected by tetrodotoxin These data suggest that neurally mediat ed serotoninergic Cl- secretion is, in part, mediated by NO. The ability of exogenous NO to induce a change in circuit current in the presence of tetr odotoxin suggests that NO is a final neurotransmitter in this neural-mucosa l reflex and therefore acts directly on the enterocyte to induce secretion.