Iwamoto I
Arerugi. 1989 Mar;38(3):239-45.
To determine the mechanism by which substance P (SP) increases vascular permeability, we examined the potency of SP and SP fragments in inducing plasma extravasation in guinea pig skin, the effects of a histamine H1 antagonist and a muscarinic antagonist on the response, the effects of SP antagonists on the response, and the specificity of tachykinin-induced tachyphylaxis of the response. SP-induced plasma extravasation of the skin was C-terminal hexapeptide-dependent. Neither a histamine H1 antagonist nor a muscarinic antagonist inhibited the response. Two SP antagonists, which have been shown to be the most potent ones in other systems, elicited plasma extravasation in the skin by themselves, but they did not inhibit SP-induced plasma extravasation. Tachyphylaxis of SP-induced plasma extravasation was induced by intradermal preinjection of SP concentration-dependently. However, preinjection of neurokinin A or neurokinin B did not affect SP-induced plasma extravasation. We conclude that SP directly increases vascular permeability through NK-1 (SP-P) receptors in guinea pig skin.
为确定P物质（SP）增加血管通透性的机制，我们检测了SP及其片段诱导豚鼠皮肤血浆外渗的效力、组胺H1拮抗剂和毒蕈碱拮抗剂对该反应的影响、SP拮抗剂对该反应的影响以及速激肽诱导的该反应快速耐受的特异性。SP诱导的皮肤血浆外渗依赖于C末端六肽。组胺H1拮抗剂和毒蕈碱拮抗剂均未抑制该反应。两种SP拮抗剂在其他系统中已被证明是最有效的，它们自身可引起皮肤血浆外渗，但不抑制SP诱导的血浆外渗。皮内预注射SP可浓度依赖性地诱导SP诱导的血浆外渗快速耐受。然而，预注射神经激肽A或神经激肽B不影响SP诱导的血浆外渗。我们得出结论，在豚鼠皮肤中，SP通过NK-1（SP-P）受体直接增加血管通透性。
