Two types of relaxation due to capsaicin in the guinea pig isolated ileum

The relaxant effect of capsaicin was investigated on isolated segments of guinea pig ileum precontracted by histamine. Two types of relaxation could be distinguished. Low concentrations of capsaicin (0.033-3.3 microM) caused partial relaxation (type I) which was prevented by in vitro desensitization to capsaicin or by extrinsic denervation and reduced by tachyphylaxis to calcitonin gene-related peptide. At higher concentrations (10-100 microM) capsaicin caused relaxation (type II) to the baseline; this effect was insensitive to capsaicin desensitization or extrinsic denervation. Neither type of relaxation was inhibited by tetrodotoxin or by alpha- and beta-adrenoceptor antagonists. We suggest that type I relaxation results from a specific effect of capsaicin on extrinsic sensory neurones of the gut while type II represents a non-specific smooth muscle depressant effect. Intrinsic enteric neurones are not involved in these effects.