Tachykinin-induced contractions in the circular muscle of guinea pig ileum.
Actions of substance P (SP, 10(-9) to 10(-6) M), neurokinin A (NKA, 10(-9) to 10(-6) M) and neurokinin B (NKB, 10(-10) to 10(-6) M) in the circular muscle of guinea pig ileum were investigated in segment and strip preparations, in which methacholine produced similar contractions. In the segment preparations, three tachykinins produced repeatedly occurring twitch-like contractions. Their efficacies were similar with the same maximal contractions, but their potencies were different (NKB > NKA = SP). Latency (38 sec) was observed before the initiation of contractions in response to NKA, but not to SP or NKB. Atropine (10(-6) M) and tetrodotoxin (3 x 10(-7) M) did not affect NKA-induced contractions, but inhibited SP- and NKB-induced contractions; the dose-response curves for SP and NKB were rightwardly shifted by atropine. The treatment with atropine brought out latency in the responses for NKB. In the strip preparations, SP did not substantially induce concentrations, but NKA and NKB produced twitch-like contractions after latent periods of 28 and 36 sec, respectively. The efficacy of NKA was similar to that in segment preparations, while that of NKB was much lower in strip preparations. Unlike in segment preparations, atropine did not inhibit contractions induced by the two tachykinins in strip preparations. These results suggest that tachykinins induce contractions through myogenic and neurogenic mechanisms, the latter of which may be inoperative in strip preparations.
Suzuki
N
N
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
Mizuno
K
K
Gomi
Y
Y
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006168:Guinea Pigs; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D015288:Neurokinin A / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013373:Substance P / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
D001713:Biphenyl Compounds; D006993:Hypnotics and Sedatives; D010456:Peptides, Cyclic; D015320:Tachykinins; C075570:FK 224; D013373:Substance P; D013779:Tetrodotoxin; D001285:Atropine; D015288:Neurokinin A; D015287:Neurokinin B; C066892:CP 96345