Relaxant effect of capsazepine in the isolated rat ileum

Abstract.

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^–8–3×10^–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 ω-conotoxin GVIA (3×10^–8 M) nor the Na⁺ channel blocker tetrodotoxin (3×10^–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 3×10^–4 M), apamin (10^–7 M), methysergide (10^–6 M), the calcitonin gene-related peptide (CGRP) antagonist hCGRP 8–37 (1.5×10^–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.