Vol. 279, Issue 3, G567-G574, September 2000
Role of cGMP as a mediator of nerve-induced motor functions of
the opossum esophagus
W.
Shahin,
J. A.
Murray,
E.
Clark, and
J. L.
Conklin
Department of Internal Medicine, University of Iowa College of
Medicine and Department of Veterans Affairs Medical Center, Iowa
City, Iowa 52242
Stimulation of esophageal nerves produces
biphasic relaxation of the lower esophageal sphincter (LES) and an off
response of circular esophageal muscle. Previously, we proposed that
cGMP mediates nerve-induced hyperpolarization 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 transducers,
placed in tissue baths containing oxygenated Krebs solution at 37°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, antagonized the off response,
shortened its latency, and blocked the first phase of LES relaxation.
ODQ also antagonized LES relaxation by exogenous nitric 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-induced
LES relaxation is not mediated by cGMP and therefore do not support the
hypothesis that VIP produces LES relaxation by causing the generation
of NO.
nitric oxide; gastrointestinal motility; smooth muscle; enteric
nervous system; vasoactive intestinal polypeptide; guanylyl
cyclase
