Capsaicin and bradykinin-induced substance P-ergic responses in the iris sphincter muscle of the rabbit.

Exogenously applied capsaicin and bradykinin produced contractile responses in the rabbit iris sphincter muscle and responses were suppressed remarkably by [D-Pro2, D-Trp7,9]-substance P, a substance P antagonist, and disappeared in trigeminally denervated preparations. Thus, the responses to capsaicin or bradykinin were considered to be mediated by substance P released from the trigeminal nerve. Repetitive application of capsaicin or bradykinin produced a gradual decline in the responses, thereby indicating the development of tachyphylaxis. Furthermore, bradykinin failed to induce any response after the development of capsaicin-induced tachyphylaxis, but after the development of tachyphylaxis to bradykinin, responses to capsaicin persisted. Electrical transmural stimulation produced cholinergic and substance P-ergic responses in the rabbit iris sphincter muscle. Substance P-ergic response to electrical transmural stimulation also was abolished after development of tachyphylaxis to capsaicin, but not to bradykinin. The contractile response to exogenously applied substance P was not affected by the development of tachyphylaxis to capsaicin and bradykinin. These results suggest that capsaicin and bradykinin produce substance P-ergic contractile responses mediated by the trigeminal nerve and that the mechanisms of action differ between the two drugs. These effects of capsaicin and bradykinin are discussed in relation to occurrence of neurogenic inflammation in the eye.