Use of NK1 knockout mice to analyze substance P-induced edema formation

被引:62
作者
Cao, T
Gerard, NP
Brain, SD
机构
[1] Kings Coll London, Sch Biomed Sci, Pharmacol Grp, London SW3 6LX, England
[2] Kings Coll London, Sch Biomed Sci, Vasc Biol Res Ctr, London SW3 6LX, England
[3] Childrens Hosp, Perlmutter Lab, Boston, MA 02115 USA
关键词
neurokinin-1; receptor; substance P; neurokinin-1 knockout mouse; edema formation; rat skin; tachykinins; neurokinins;
D O I
10.1152/ajpregu.1999.277.2.R476
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
The mechanisms involved in tachykinin-induced neurokinin-1 (NK1) receptor-mediated edema formation have been studied in anesthetized wild-type and NK1 knockout mice. Intradermally injected substance P (30-300 pmol), NK1 agonists septide (3-30 pmol) and GR-73632 (3-30 pmol), and the mast cell-degranulating agent, compound 48/80 induced dose-dependent edema in wild-type skin, measured by the accumulation of intravenously injected I-125-labeled albumin. Septide was 3-10 X more potent than substance P. The tachykinins were inactive in knockout mice, but compound 48/80 induced a significantly greater edema (P < 0.05) than that observed in paired wild-type mice. Capsaicin (which releases endogenous neuropeptides) and exogenous tachykinins induced edema formation, which was reduced by the mast cell amine histamine ill antagonist mepyramine (P < 0.05). These findings confirm that tachykinins mediate edema formation via the NK1 receptor and provide direct evidence that the septide-sensitive binding site is on the NK1 receptor. Furthermore, results suggest that edema induced by the tachykinins, although totally dependent on NK1 receptor-mediated mechanism, contains a mast cell-dependent component. The evidence is in keeping with an NK1 receptor on mast cells.
引用
收藏
页码:R476 / R481
页数:6
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