Effect of tachykinins on the acetylcholine output stimulated by nicotine from guinea-pig bladder.
Effects of tachykinins on contractile responses and acetylcholine release evoked by nicotine were determined by isotonic transducer and radioimmunoassay. A sympathetic nerve blocker guanethidine and tachykinin antagonist, [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-substance P (rpwwL-SP) partially inhibited the acetylcholine release evoked by nicotine to much the same degree. In preparations treated with rpwwL-SP to block the tachykinin receptors, guanethidine had no effect on the response to nicotine and vice versa, suggesting an exclusive contribution of the sympathetic nerve communications to the action of tachykinins. A concentration response curve to neurokinin A but not SP methyl ester or Tyr0-neurokinin B was shifted to the left after cholinesterase inhibition with methanesulphonyl fluoride (MSF) and was partially inhibited by atropine. In the presence of guanethidine, an acetylcholine output by nicotine was facilitated in the presence of neurokinin A (10 nM) but not SP methyl ester (10 nM) or senktide (10 nM). These results indicate that acetylcholine release evoked by nicotine is increased by the coordinated action of sympathetic nerves and tachykinins. Tachykinin receptor subtype involved in acetylcholine release is NK2.
Shinkai
M
M
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Takayanagi
I
I
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D005260:Female; D006145:Guanethidine / Q000494:pharmacology; D006168:Guinea Pigs; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors / Q000502:physiology; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D015320:Tachykinins / Q000037:antagonists & inhibitors; D013779:Tetrodotoxin / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*
D006584:Hexamethonium Compounds; D018039:Receptors, Tachykinin; D015320:Tachykinins; D013373:Substance P; D018738:Hexamethonium; D013779:Tetrodotoxin; D009538:Nicotine; C038073:substance P, Arg(1)-Pro(2)-Trp(7),(9)-LeuNH(2)(11)-; D000109:Acetylcholine; D006145:Guanethidine