Carruette A, Moussaoui S M, Champion A, Cottez D, Goniot P, Garret C
Rhone-Poulenc Rorer, Centre de Recherches de Vitry-Alfortville, Vitry-sur-Seine, France.
Neuropeptides. 1992 Dec;23(4):245-50. doi: 10.1016/0143-4179(92)90131-f.
We describe the effects of RP 67580, a new non-peptide substance P (SP) antagonist, on tachykinin-induced contractions of guinea-pig ileum, trachea and urinary bladder, rabbit pulmonary artery and rat portal vein. All NK1 agonists tested (SP, Septide, SPOMe and [Pro9]SP) contracted guinea-pig ileum, trachea and urinary bladder (pD2 = 7.5 to 9.1), but they had no effect on rabbit pulmonary artery or rat portal vein (pD2 < 6). RP 67580 inhibited these effects: guinea-pig ileum, pA2 = 7.1 to 7.6; guinea-pig trachea and urinary bladder, pKB = 6.3 to 6.8. The difference in RP 67580 activity in these tissues might be due to the existence of subtypes of NK1 receptors. RP 67580 (1 microns) did not affect the contractions induced by the two NK2 agonists, NKA and [Lys5, MeLeu9, Nle10]NKA(4-10) (pA2 < 6), except in guinea-pig ileum (pA2 = 7.3-7.5) where these two NK2 agonists interact apparently with NK1 receptors. In the tissue preparations used, RP 67580 (1 micron) was without effect on contractions induced by the NK3 agonists: NKB and senktide. These results indicate the high selectivity for NK1 receptors of RP 67580. In all cases, similar results were obtained with another non-peptide SP antagonist, (+/-) CP-96,345. The present work provides further evidence that RP 67580 and (+/-) CP-96,345 exert in vitro a potent, selective and competitive antagonistic action on NK1 receptors and suggests the existence of at least two distinct NK1 receptor subtypes in some guinea-pig peripheral organs.
我们描述了一种新型非肽类P物质（SP）拮抗剂RP 67580对豚鼠回肠、气管和膀胱、兔肺动脉以及大鼠门静脉中速激肽诱导收缩的影响。所有测试的NK1激动剂（SP、Septide、SPOMe和[Pro9]SP）均可使豚鼠回肠、气管和膀胱收缩（pD2 = 7.5至9.1），但对兔肺动脉或大鼠门静脉无作用（pD2 < 6）。RP 67580可抑制这些作用：豚鼠回肠，pA2 = 7.1至7.6；豚鼠气管和膀胱，pKB = 6.3至6.8。这些组织中RP 67580活性的差异可能归因于NK1受体亚型的存在。RP 67580（1微摩尔）不影响两种NK2激动剂NKA和[Lys5，MeLeu9，Nle10]NKA(4 - 10)诱导的收缩（pA2 < 6），但在豚鼠回肠中除外（pA2 = 7.3 - 7.5），在豚鼠回肠中这两种NK2激动剂显然与NK1受体相互作用。在所使用的组织制剂中，RP 67580（1微摩尔）对NK3激动剂NKB和senktide诱导的收缩无作用。这些结果表明RP 67580对NK1受体具有高度选择性。在所有情况下，另一种非肽类SP拮抗剂(+/-) CP - 96,345也得到了类似结果。本研究进一步证明RP 67580和(+/-) CP - 96,345在体外对NK1受体发挥强效、选择性和竞争性拮抗作用，并提示在一些豚鼠外周器官中存在至少两种不同的NK1受体亚型。
