Pharmacological evidence for the possible coexistence of multiple receptor sites for mammalian tachykinins in rabbit iris sphincter smooth muscle.

Contractile responses to neurokinin alpha and neurokinin beta were characterized and compared with those to substance P (a SP-P agonist) and eledoisin (a SP-E agonist) in isolated rabbit iris sphincter. Neurokinin alpha and neurokinin beta as well as substance P and eledoisin produced atropine- and tetrodotoxin-resistant contractions of the iris sphincter in nanomolar concentrations, and the rank order of sensitivity was eledoisin greater than substance P = neurokinin alpha = neurokinin beta. After prolonged cold-storage of the preparations, responses to capsaicin, a releaser of tachykinins from sensory nerve endings, were nearly absent, but responses of considerable magnitude to carbachol and the tachykinins persisted. On wash-out of the tachykinins, responses faded at characteristic rates (neurokinin alpha greater than eledoisin greater than neurokinin beta much greater than substance P). From the Schild analyses, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P, a potent substance P antagonist, competitively antagonized the response to substance P, had no significant effect on the response to neurokinin beta, and antagonized the response to neurokinin alpha and eledoisin in a more complex manner. Taken together, these results suggest that there coexist multiple receptor sites for mammalian tachykinins in rabbit iris sphincter smooth muscle.