Mechanism of action of nicotine in isolated urinary bladder of guinea-pig: involvement of tachykinin(s) released by nicotine in the drug's sympathomimetic effect.
A sympathetic neurone blocking drug, guanethidine, and a tachykinin antagonist, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P (rpwwL-SP), partially inhibited the contractile response to nicotine to the same degree in the isolated detrusor strips of guinea-pig urinary bladder. Application of rpwwL-SP completely abolished the inhibitory effect of guanethidine on the nicotine-induced contraction, suggesting that the tachykinin(s)-ergic transmission might be involved in the sympathomimetic effect of nicotine. Conversely, when the preparation was treated with guanethidine to block release of a mediator from the sympathetic nerve, the inhibitory effect of rpwwL-SP was diminished, suggesting an exclusive contribution of the sympathetic nerve communications to the action of the tachykinin(s). We previously suggested that nicotine may release acetylcholine and ATP to contract the detrusor strips, and that acetylcholine output may be increased by an unknown substance released from the sympathetic nerve by nicotine. In preparations treated with atropine, rpwwl-SP had no effect on the nicotine-induced contraction. The concentration-response curves for carbachol and ATP were not influenced by rpwwl-SP. After tachyphylaxis to capsaicin developed, the nicotine-induced contraction was not affected. It is suggested that in guinea-pig detrusor, tachykinin(s) from capsaicin-insensitive sites is (are) involved in the excitatory sympathomimetic effect of nicotine, and that the tachykinin(s) behave(s) as a modulator finally to increase the acetylcholine output from the parasympathetic cholinergic nerve.
Hisayama
T
T
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Shinkai
M
M
Takayanagi
I
I
Toyoda
T
T
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D005260:Female; D006145:Guanethidine / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation; D009538:Nicotine / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology; D013566:Sympathomimetics; D009435:Synaptic Transmission / Q000187:drug effects; D015320:Tachykinins / Q000378:metabolism / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation
D011976:Receptors, Muscarinic; D013566:Sympathomimetics; D015320:Tachykinins; D013373:Substance P; D009538:Nicotine; D000255:Adenosine Triphosphate; D002217:Carbachol; D006145:Guanethidine