Differential effects of nitric oxide donors on basal and electrically evoked release of acetylcholine from guinea-pig myenteric neurones.
1. The effects of the nitric oxide (NO) donors, 3-morpholino-sydnonimine (SIN-1), S-nitroso-N-acetylpenicillamine (SNAP) and sodium nitroprusside on basal and electrically evoked release of [3H]-acetylcholine were studied in myenteric plexus longitudinal muscle preparations of the guinea-pig small intestine preincubated with [3H]-choline. 2. The NO donors concentration-dependently increased basal release of [3H]-acetylcholine. The increase in release was calcium-dependent and was prevented in the presence of tetrodotoxin. Superoxide dismutase (150 u ml-1) potentiated the effect of SIN-1. The selective inhibitor of soluble guanylyl cyclase, 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ, 0.01-1 microM), antagonized the facilitatory effect of SNAP. 8-Bromo cyclic GMP and the cyclic GMP-specific phosphodiesterase inhibitor, zaprinast (both 0.1-1 mM), also enhanced basal [3H]-acetylcholine release. The effect of 10 microM SNAP was significantly enhanced in the presence of zaprinast. 3. The NO donors concentration-dependently inhibited the electrically evoked release of [3H]-acetylcholine, whereas 8-bromo cyclic GMP and zaprinast enhanced the evoked release. The inhibition of acetylcholine release by SNAP was not affected by ODQ (0.01-1 microM). 4. It is concluded that NO stimulates basal acetylcholine release from myenteric neurones through activation of guanylyl cyclase. In addition, NO inhibits the depolarization evoked release of acetylcholine by a presynaptic mechanism unrelated to cyclic GMP. The data imply that NO is not only an inhibitory transmitter to intestinal smooth muscles but also a modulator of cholinergic neurotransmission in the myenteric plexus.
Hebeiss
K
K
Department of Pharmacology, University of Mainz, Germany.
Kilbinger
H
H
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009197:Myenteric Plexus / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D000109:Acetylcholine