Some characterization of the responses to substance P and other tachykinins in rabbit iris sphincter muscle.

Contractile responses to substance P, physalaemin and eledoisin, three members of the tachykinin family, were compared and characterized in rabbit iris sphincter smooth muscle. Eledoisin and physalaemin were approximately 5 times more potent than substance P, and the maximum responses to substance P and physalaemin were about 85 percent of those to eledoisin and carbachol. The contractile responses to the three tachykinins were not affected by tetrodotoxin (3 X 10(-6) M) and atropine (10(-6) M). The contractions induced by substance P and physalaemin were well sustained even after they were thoroughly washed out, whereas the eledoisin-induced contraction was rapidly ceased by removing the agonist from the bathing medium. The sustained contraction evoked by substance P or physalaemin was strongly dependent on extracellular calcium ions. Phenoxybenzamine (2 X 10(-5) M, 10 min) selectively attenuated the response to eledoisin, but not substance P or physalaemin, and concomitant incubation with excess eledoisin (10(-7) M) significantly prevented the inhibitory effect of phenoxybenzamine. The difference between responses to eledoisin and to the other peptides, substance P and physalaemin, may suggest the existence of two different receptor subtypes for tachykinins in rabbit iris sphincter smooth muscle.