The miotic effect of substance P on the isolated rabbit iris

The effect of substance P on the rabbit iris was investigated by continuously monitoring the pupil size in vitro. Continuous perfusion with substance P caused a concentration-dependent contraction of the iridial sphincter muscle. The threshold was 2 x 10(-10) M. A concentration-response curve was made for 60 sec exposures of the iris to substance P. Blockade of muscarinic, nicotinic, alpha-, and beta-adrenergic receptors as well as blockade with the putative presynaptic substance P-blocking agent baclofen did not affect the constrictor response to substance P. Pretreatment of the rabbits with indomethacin was also without effect. No effect of substance P was seen on the isolated iridial dilator muscle. Although the miotic response to substance P was observed in a calcium-free perfusion fluid, EGTA added to calcium-free perfusate diminished the effect of substance P. The response of the iris to substance P and the time course of the response make it likely that substance P is involved in the miosis of the nerve-mediated irritative response of the eye.