Tachykinin-induced contraction of the guinea-pig isolated oesophageal mucosa is mediated by NK2 receptors

1 The tachykinin receptor present in the guinea-pig oesophageal mucosa that mediates contractile responses of the muscularis mucosae has been characte rized, using functional in vitro experiments. 2 The NK1 receptor-selective agonist, [Sar(9)(O-2)Met(11)]SP and the NK3 re ceptor-selective agonists, [MePhe(7)]-NKB and senktide, produced no respons e at submicromolar concentrations. The NK2 receptor-selective agonists, [Nl e(10)]-NKA(4-10), and GR 64,349 produced concentration-dependent contractil e effects with pot values of 8.20+/-0.16 and 8.30+/-0.15, respectively. 3 The concentration-response curve to the non-selective agonist, NKA (pD(2) =8.13+/-0.04) was shifted significantly rightwards only by the NK2 receptor -selective antagonist, GR 159.897 and was unaffected by the NK1 receptor-se lective antagonist, SR 140,333 and the NK3 receptor-selective antagonist, S E 222,200. 4 The NK2 receptor-selective antagonist, GR 159,897, exhibited an apparent competitive antagonism against the NK2 receptor-selective agonist, GR 64,34 9 (apparent pK(B) value = 9.29 +/- 0.16) and against the non-selective agon ist, NKA (apparent pK(B) value = 8.71 +/- 0.19). 5 The NK2 receptor-selective antagonist. SR 48,968 exhibited a non-competit ive antagonism against the NK1 receptor-selective agonist, [Nle(10)]-NKA(4- 10). The pK(B) value was 10.84+/-0.19. 6 It is concluded that the guinea-pig isolated oesophageal mucosa is a usef ul preparation for studying the effects of NK2 receptor-selective agonists and antagonists as the contractile responses to Various tachykinins are med iated solely by NK2 receptors.