Relaxant effect of capsazepine in the isolated rat ileum.
We have evaluated the effect of the vanilloid receptor agonists resiniferatoxin (RTX), capsaicin and piperine and of the vanilloid receptor antagonist capsazepine on the resting tone in the isolated rat ileum. Capsazepine (10(-8)-3 x 10(-5) M) produced a concentration-related relaxation (8 +/-3%-49 +/-3%) of the rat ileum. By contrast RTX (up to 10(-8) M), capsaicin (up to 10(-6) M) and piperine (up to 10(-5) M) were without effect. Pre-treatment with capsaicin [either in vivo (50 mg/kg s.c.) or in vitro (10(-6) M)] did not modify the inhibitory effect of capsazepine. The L-type Ca2+ channel antagonist nifedipine (10(-6) M), but not the N-type Ca2+ channel antagonist omega-conotoxin GVIA (3 x 10(-8) M) nor the Na+ channel blocker tetrodotoxin (3 x 10(-7) M), counteracted the inhibitory effect of capsazepine. The NK1 receptor antagonist SR 140333 (10(-7) M), the NK2 receptor antagonist SR 48968 (10(-6) M), the NK3 receptor antagonist SR 142801 (10(-7) M), atropine (10(-6) M), hexamethonium (10(-4) M), phentolamine (10(-6) M) plus propranolol (10(-6) M), N(G)-nitro- L-arginine methyl ester ( L-NAME 3 x 10(-4) M), apamin (10(-7) M), methysergide (10(-6) M), the calcitonin gene-related peptide (CGRP) antagonist hCGRP 8-37 (1.5 x 10(-6) M), the VIP antagonist hGRF 1-29 (10(-5) M) did not modify the inhibitory effect of capsazepine. Capsazepine (2.5-40 mg/kg) also decreased upper gastrointestinal transit in vivo. It is concluded that the vanilloid antagonist capsazepine has a direct relaxing effect on rat intestinal smooth muscle which could involve L-type calcium channels. We found no evidence to suggest that capsazepine is antagonizing an endogenous vanilloid.
Nocerino
Emilia
E
Department of Experimental Pharmacology, University of Naples "Federico II", via D. Montesano 49, 80131 Naples, Italy.
Izzo
Angelo A
AA
Borrelli
Francesca
F
Capasso
Francesco
F
Capasso
Raffaele
R
Pinto
Aldo
A
Sautebin
Lidia
L
Mascolo
Nicola
N
D000470:Alkaloids; D000818:Animals; D052117:Benzodioxoles; D020746:Calcium Channels, L-Type / Q000187:drug effects; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005772:Gastrointestinal Transit / Q000187:drug effects; D007082:Ileum / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug / Q000819:agonists / Q000037:antagonists & inhibitors*
D000470:Alkaloids; D052117:Benzodioxoles; D020746:Calcium Channels, L-Type; D004224:Diterpenes; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011955:Receptors, Drug; C024353:resiniferatoxin; C071423:capsazepine; D002211:Capsaicin; C008922:piperine