PHARMACOLOGICAL ANALYSIS OF RECEPTORS INVOLVED IN THE LATE, TACHYKININERGIC CONTRACTILE RESPONSE TO ELECTRICAL TRANSMURAL-STIMULATION IN ISOLATED RABBIT IRIS SPHINCTER MUSCLE

We characterized the pharmacological nature of the tachykinin receptor subtype mediating the contractile response to electrical transmural s timulation (ETS) in the isolated rabbit iris sphincter muscle preparat ion by using selective NK1-receptor antagonists, spantide and L-668,16 9, and a selective NK2-receptor antagonist, L-659,877. ETS caused a bi phasic contraction in this preparation: a rapidly developing cholinerg ic component followed by a slowly decaying tachykininergic component. The tachykininergic contractile response to ETS was effectively attenu ated by spantide and L-668,169, but only slightly by L-659,877, indica ting that the tachykinin receptors mediating ETS-induced contraction a re of the NK1 type. In the same preparation, the contractile activity of substance P (SP) was slightly more potent than that of neurokinin A (NKA). Unlike in other tissues rich in NK1-receptor subtypes, spantid e and L-668,169 antagonized the contractile response to NKA more effec tively than that to SP, and the reverse was observed for L-659,877. Th ese results strongly suggest that the tachykininergic contraction indu ced by ETS in the rabbit iris sphincter preparation is mediated by NK1 -receptors which are activated by endogenously released NKA.