Inoue H, Nagata N, Koshihara Y
Research Laboratory, Minophagen Pharmaceutical Co., Kanagawa, Japan.
Inflamm Res. 1996 Jul;45(7):316-23. doi: 10.1007/BF02252943.
The involvement of tachykinin receptors in skin inflammation induced by substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) was investigated in mouse ears. Intradermal injection of tachykinins (0.1-100 pmol/site) into the ear skin produced oedema formation. RP 67580 (ED50: 0.34 mg/kg, i.v.) and SR 140333 (ED50: 0.19 mg/kg, i.v.), the non-peptide NK1 receptor antagonists, inhibited SP-induced oedema. SR 140333 was also effective in preventing NKA- and NKB-induced oedema. SR 48968 (1 mg/kg, i.v.), a non-peptide NK2 antagonist, induced a significant inhibition of NKA-induced oedema but had no effect on the response to SP and NKB. SR 142801 (3 mg/kg, i.v.), a non-peptide NK3 antagonist, prevented only NKB-induced oedema. In contrast, phosphoramidon (0.1 and 0.5 mg/kg, i.v.), an endopeptidase inhibitor, enhanced the oedema response to tachykinins. SR 140333, SR 48968, and SR 142801 blocked the enhancement by phosphoramidon of the response to SP, NKA, and NKB, respectively. Plasma extravasation in ear skin was induced by i.v. injection of tachykinins (0.7-17.6 nmol/kg). RP 67580 (ED50: 0.15 mg/kg, i.v. for SP) and SR 140333 (ED50: 14.3 micrograms/kg, i.v. for SP) inhibited tachykinin-induced plasma extravasation in ear skin. However, SR 48968 and SR 140281 had no effect on the vascular response to tachykinins. Chlorpheniramine (4 mg/kg, i.v.), a histamine H1 blocker, inhibited the response to local SP but not to i.v. SP. These results suggest that in addition to the NK1 receptors, functional NK2 and NK3 receptors may participate in the oedema response to local NKA and NKB in the ear skin. However, it appears that NK1 receptors on blood vessels are involved predominantly in plasma extravasation induced by i.v. tachykinins in the ear.
研究了速激肽受体在P物质（SP）、神经激肽A（NKA）和神经激肽B（NKB）诱导的小鼠耳部皮肤炎症中的作用。向耳部皮肤皮内注射速激肽（0.1 - 100 pmol/部位）可导致水肿形成。非肽类NK1受体拮抗剂RP 67580（静脉注射半数有效量：0.34 mg/kg）和SR 140333（静脉注射半数有效量：0.19 mg/kg）可抑制SP诱导的水肿。SR 140333在预防NKA和NKB诱导的水肿方面也有效。非肽类NK2拮抗剂SR 48968（静脉注射1 mg/kg）可显著抑制NKA诱导的水肿，但对SP和NKB诱导的反应无影响。非肽类NK3拮抗剂SR 142801（静脉注射3 mg/kg）仅能预防NKB诱导的水肿。相反，内肽酶抑制剂磷酰胺素（静脉注射0.1和0.5 mg/kg）可增强对速激肽的水肿反应。SR 140333、SR 48968和SR 142801分别阻断了磷酰胺素对SP、NKA和NKB反应的增强作用。静脉注射速激肽（0.7 - 17.6 nmol/kg）可诱导耳部皮肤血浆外渗。RP 67580（静脉注射SP时半数有效量：0.15 mg/kg）和SR 140333（静脉注射SP时半数有效量：14.3 μg/kg）可抑制速激肽诱导的耳部皮肤血浆外渗。然而，SR 48968和SR 140281对速激肽引起的血管反应无影响。组胺H1受体阻滞剂氯苯那敏（静脉注射4 mg/kg）可抑制对局部SP的反应，但对静脉注射SP无影响。这些结果表明，除NK1受体外，功能性NK2和NK3受体可能参与耳部皮肤对局部NKA和NKB的水肿反应。然而，血管上的NK1受体似乎主要参与静脉注射速激肽诱导的耳部血浆外渗。
