Effects of neurokinin A, substance P and electrical stimulation on the rabbit iris sphincter muscle

A mammalian tachykinin, neurokinin A (NKA), and its analogs produced concentration-dependent contractions in the isolated rabbit iris sphincter muscle. Their potencies were slightly less than substance P (SP) but the maximal efficacies were much the same as seen with SP, except that the times required for the development of the contraction and for the recovery to the original level after washout were more rapid than in the case of SP. Although preceding exposure to SP reduced the subsequent responses to SP, NKA, carbachol, electrical stimulation and capsaicin, the exposure to NKA resulted in no such desensitization in the subsequent responses. Also, no reduction in the responses to NKA, SP and carbachol was observed in the preparations which had been exposed to capsaicin beforehand. The contractile responses to NKA and its analogs were more effectively inhibited by [D-Pro2, D-Trp7,9]-SP than was the response to SP. [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-SP also inhibited the responses to NKA and its analogs but had no effect on the response to SP. Both SP-antagonists inhibited the noncholinergic, nonadrenergic contractile response to electrical transmural stimulation. These results indicate that NKA and its analogs are potent contractile tachykinins in the rabbit iris sphincter muscle and that the mode of action differs somewhat from that seen with SP. We propose that noncholinergic, nonadrenergic contraction induced by electrical transmural stimulation is mediated predominantly by NKA rather than by SP, even though both these compounds are released concomitantly from the trigeminal nerve.