Role of cGMP as a mediator of nerve-induced motor functions of the opossum esophagus.
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 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, 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.
Shahin
W
W
Department of Internal Medicine, University of Iowa College of Medicine and Department of Veterans Affairs Medical Center, Iowa City, Iowa 52242, USA.
Murray
J A
JA
Clark
E
E
Conklin
J L
JL
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism*; D017615:Enteric Nervous System / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004943:Esophagogastric Junction / Q000294:innervation* / Q000502:physiology*; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000201:enzymology; D009130:Muscle, Smooth / Q000166:cytology / Q000294:innervation / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D009893:Opossums; D010069:Oxadiazoles / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D010276:Parasympatholytics; D011810:Quinoxalines; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D001285:Atropine; D006162:Guanylate Cyclase; D006152:Cyclic GMP