Pharmacological Analysis of Receptors Involved in the Late, Tachykininergic Contractile Response to Electrical Transmural Stimulation in Isolated Rabbit Iris Sphincter Muscle

抄録

We characterized the pharmacological nature of the tachykinin receptor subtype mediating the contractile response to electrical transmural stimulation (ETS) in the isolated rabbit iris sphincter muscle preparation by using selective NK₁-receptor antagonists, spantide and L-668, 169, and a selective NK₂-receptor antagonist, L-659, 877. ETS caused a biphasic contraction in this preparation: a rapidly developing cholinergic component followed by a slowly decaying tachykininergic component. The tachykininergic contractile response to ETS was effectively attenuated by spantide and L-668, 169, but only slightly by L-659, 877, indicating that the tachykinin receptors mediating ETS-induced contraction are 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, spantide and L-668, 169 antagonized the contractile response to NKA more effectively than that to SP, and the reverse was observed for L-659, 877. These results strongly suggest that the tachykininergic contraction induced by ETS in the rabbit iris sphincter preparation is mediated by NK₁-receptors which are activated by endogenously released NKA.