Tachykinin receptors of the NK2 type involved in the acetylcholine release by nicotine in guinea-pig bladder.
1. The effects of guanethidine and tachykinins on nicotine- and electrical stimulation-induced cholinoceptor responses were studied in isolated urinary bladder from the guinea-pig. 2. Acetylcholine release and the contractile response stimulated by nicotine were partially reduced by a sympathetic nerve blocker, guanethidine. Neurokinin A (but not substance P methyl ester or senktide) enhanced both acetylcholine release and contraction by nicotine in the presence of guanethidine. 3. Frequency-contraction curves (1 to 50 Hz) for electrical field stimulation (EFS) were partially reduced by atropine (1 microM), and after desensitization to alpha,beta-methylene adenosine 5'-triphosphate, the atropine-resistant contraction to EFS was completely abolished. Guanethidine, the tachykinin antagonist [D-Arg1, D-Pro2, Trp7,9, Leu11]-substance P and application of neurokinin A or substance P did not change the contractile response to EFS. Preganglionic nerve stimulation (5 Hz and 20 Hz) also evoked a similar response to EFS and was not influenced at all by guanethidine or neurokinin A. 4. We conclude that the ability of nicotine to release acetylcholine is enhanced both by endogenous tachykinins (probably released from sympathetic nerves) and by exogenously applied tachykinins as a result of interaction with NK2 receptors in the urinary bladder.
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
M
M
Shinkai
I
I
Takayanagi
T
T
Kato
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D004558:Electric Stimulation; D005724:Ganglia / Q000502:physiology; D006145:Guanethidine / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D011863:Radioimmunoassay; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D009538:Nicotine; D000109:Acetylcholine; D006145:Guanethidine