Role of cGMP as a mediator of nerve-induced motor functions of the opossumesophagus

Stimulation of esophageal nerves produces biphasic relaxation of the lower esophageal sphincter (LES) and an off response of circular esophageal muscl e. Previously, we proposed that cGMP mediates nerve-induced hyperpolarizati on of circular LES muscle but not LES relaxation. These experiments explore whether cGMP mediates LES relaxation or the off response. Strips of muscle from the opossum esophagus and LES were connected to force-displacement tr ansducers, placed in tissue baths containing oxygenated Krebs solution at 3 7 degrees C, and stimulated by an electrical field. 1H-[1,2,4]oxadiazolo-[4 ,3-a]quinoxalin-1-one (ODQ), a selective inhibitor of guanylyl cyclase, ant agonized the off response, shortened its latency, and blocked the first pha se of LES relaxation. ODQ also antagonized LES relaxation by exogenous nitr ic oxide (NO) but not relaxations by vasoactive intestinal polypeptide (VIP ). Part of the nerve-induced LES relaxation and the off response appear to be mediated by the second messenger cGMP. These studies indicate that VIP-i nduced LES relaxation is not mediated by cGMP and therefore do not support the hypothesis that VIP produces LES relaxation by causing the generation o f NO.