Inoue H, Nagata N, Koshihara Y
Research Laboratory, Minophagen Pharmaceutical Co., Kanagawa, Japan.
Inflamm Res. 1996 Jun;45(6):303-7. doi: 10.1007/BF02280996.
We examined the effect of SR 140333, a nonpeptide NK1 receptor antagonist, FK 888, a peptide NK1 antagonist, and SR 142801, a non-peptide NK3 antagonist, on ear oedema induced by topical application of capsaicin (250 micrograms/ear) in mice. SR 140333 (ED50:39 micrograms/kg, i.v.) dose-dependently inhibited the oedema response to capsaicin, whereas FK 888 (1.0 mg/kg, i.v.) and SR 142801 (3.0 mg/kg, i.v.) had no effect. Furthermore, SR 140333 significantly (p < 0.001) suppressed ear oedema in response to intradermal injection of substance P (SP) (100 pmol/site) by i.v. administration (0.1 mg/kg,) and co-injection (50 pmol/site). In contrast, FK 888 (1.0 mg/kg, i.v. and 500 pmol/site) was ineffective in the response to SP. The present results suggest that the difference in effects of the two NK1 receptor antagonists on the oedema response to capsaicin is due to species differences in affinities for the NK1 receptor in the mouse skin. Moreover, it seems unlikely that the NK3 receptor is involved primarily in capsaicin-induced mouse ear oedema.
我们研究了非肽类NK1受体拮抗剂SR 140333、肽类NK1拮抗剂FK 888以及非肽类NK3拮抗剂SR 142801对小鼠局部应用辣椒素（250微克/耳）诱导的耳部水肿的影响。SR 140333（静脉注射半数有效剂量：39微克/千克）剂量依赖性地抑制对辣椒素的水肿反应，而FK 888（静脉注射1.0毫克/千克）和SR 142801（静脉注射3.0毫克/千克）无作用。此外，SR 140333通过静脉给药（0.1毫克/千克）和联合注射（50皮摩尔/部位）显著（p<0.001）抑制了对皮内注射P物质（SP）（100皮摩尔/部位）的耳部水肿。相比之下，FK 888（静脉注射1.0毫克/千克和500皮摩尔/部位）对SP反应无效。目前的结果表明，两种NK1受体拮抗剂对辣椒素诱导的水肿反应的作用差异是由于对小鼠皮肤中NK1受体亲和力的种属差异。此外，NK3受体似乎不太可能主要参与辣椒素诱导的小鼠耳部水肿。
