Nitric oxide increases stimulation-evoked acetylcholine release from rat hippocampal slices by a cyclic GMP-independent mechanism.
Nitric oxide (NO) is an endothelium-derived relaxing factor and its main mechanism of action is activation of soluble guanylyl cyclase. NO and NO-related compounds have been reported to affect several neuronal functions in the central nervous system. In this study, we investigated the effects of NO donors (sodium nitroprusside (SNP) and (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409)) on acetylcholine (ACh) release from rat hippocampal slices. SNP (10(-5) M) and FK409 (10(-4) M) increased electrical stimulation-evoked ACh release without affecting basal release. As dibutyryl cyclic GMP inhibited stimulation-evoked ACh release, the effects of these NO donors were not due to soluble guanylyl cyclase activation. Atropine increased stimulation-evoked ACh release by blocking presynaptic muscarinic autoreceptors, and SNP increased stimulation-evoked ACh release in the presence of atropine, suggesting that SNP and atropine increase stimulation-evoked ACh release by different mechanisms. The present results indicate that NO enhances some part of the excitation-secretion coupling pathway without inducing ACh release directly and these effects are mediated by cyclic GMP-independent mechanism.
Suzuki
T
T
Department of Pharmacology, Kyoritsu College of Pharmacy, Minato-ku, Tokyo, Japan. suzuki-tk@kyoritsu-ph.ac.jp
Nakajima
K
K
Fujimoto
K
K
Fujii
T
T
Kawashima
K
K
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D006152:Cyclic GMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005292:Ferricyanides / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology
D005292:Ferricyanides; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D006152:Cyclic GMP; D000109:Acetylcholine; C028033:potassium ferricyanide