Nitric oxide inhibits smooth muscle responses evoked by cholinergic nerve stimulation in the guinea pig gastric fundus.
In circular smooth muscle tissues of the guinea pig gastric fundus, transmural nerve stimulation (TNS) evoked an atropine-sensitive cholinergic excitatory junction potential (e.j.p.) and, after inhibiting the e.j.p. with atropine, an apamin-sensitive nonadrenergic noncholinergic (NANC) inhibitory junction potential (i.j.p.). The amplitude of e.j.p.s was similar when the frequency of TNS was low (<0.5 Hz), but it decreased successively (depression phenomenon) when the frequency was high (>1 Hz). The depression phenomenon was attenuated after inhibiting the production of nitric oxide (NO) with N(omega)-nitro-L-arginine (NOLA), but was not altered by inhibiting the i.j.p. with apamin. The e.j.p.s were increased in amplitude by the inhibition of cholinesterase activity, but they were decreased by NO produced from SNP with no alteration of their depression phenomenon. Isometric twitch contractions were depressed during high-frequency TNS. NOLA caused an increase in the amplitude of twitch contractions and the attenuation of their depression that changed the transient contraction produced by high-frequency TNS (1 Hz) to a tetanic one. SNP reduced the amplitude of twitch contractions, with no alteration of the depression phenomena. Contractions produced by low concentrations of acetylcholine, but not by high concentrations, were attenuated by SNP, with no alteration of the membrane depolarization. The results suggest that NO produced during TNS has inhibitory actions on cholinergic transmission; the depression of e.j.p.s is mainly prejunctional events, and the depression of mechanical responses is mainly postjunctional events.
Yoneda
S
S
Department of Physiology, Nagoya City University Medical School, Nagoya, 467-8601 Japan.
Suzuki
H
H
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005748:Gastric Fundus / Q000294:innervation / Q000502:physiology; D006168:Guinea Pigs; D007537:Isometric Contraction / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000294:innervation* / Q000502:physiology*; D009388:Neostigmine / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D010276:Parasympatholytics; D009599:Nitroprusside; D019335:Nitroarginine; D001030:Apamin; D009569:Nitric Oxide; D009388:Neostigmine; D001285:Atropine; D000109:Acetylcholine