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

Abstract

Background: Serotonin (5-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– secretion is ultimately mediated by nitric oxide (NO). Methods: Unstripped sheets of rat distal colon were mounted in Ussing chambers and short-circuited. The 5-HT3 receptor agonist, 2-methyl-5-HT, was added in the absence and presence of the NO synthase inhibitor, L-NAME. Companion studies involved the addition of sodium nitroprusside to tissue that was 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 nitroprusside caused a change in circuit current over baseline in 5 minutes. The addition of tetrodotoxin did not significantly alter the change in circuit 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 is inhibited by an NO synthase inhibitor. Exogenous NO mimics this response, which is unaffected by tetrodotoxin. These data suggest that neurally mediated 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 tetrodotoxin suggests that NO is a final neurotransmitter in this neural-mucosal reflex and therefore acts directly on the enterocyte to induce secretion. (Surgery 2000;128:240-5.)