FURTHER DEMONSTRATION THAT [PRO9]-SUBSTANCE-P IS A POTENT AND SELECTIVE LIGAND OF NK-1 TACHYKININ RECEPTORS

被引:34
作者
PETITET, F
BEAUJOUAN, JC
SAFFROY, M
TORRENS, Y
CHASSAING, G
LAVIELLE, S
BESSEYRE, J
GARRET, C
CARRUETTE, A
GLOWINSKI, J
机构
[1] UNIV PARIS 06,CNRS,UA 493,CHIM LAB,PARIS,FRANCE
[2] RHONE POULENC,VITRY,FRANCE
关键词
TACHYKININS; NK-1 SELECTIVE AGONIST; PRO9]-SUBSTANCE-P; BINDING STUDIES; AUTORADIOGRAPHY; BIOLOGICAL ACTIVITIES;
D O I
10.1111/j.1471-4159.1991.tb02004.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Previous studies have indicated that [Pro9]-substance P ([Pro9]-SP) possesses very good affinity for NK-1 binding sites and that, in contrast to substance P, it interacts selectively with these sites. Therefore, [H-3][Pro9]-SP (75 Ci/mmol) was synthesized in order to study its binding to membranes of the rat brain. Specific binding of [H-3][Pro9]-SP (75% of total binding) was temperature-dependent, saturable, and reversible. Scatchard analysis and Hill plots revealed the existence of a single population of noninteracting binding sites (K(D) and B(max) values: 1.48 nM and 29.7 fmol/mg of protein, respectively). Competition studies with several tachykinins and analogues indicated that the pharmacological profile of [H-3][Pro9]-SP binding sites is identical to that of NK-1 binding sites. Rat brain sections labeled with either [H-3][Pro9]-SP or [H-3]SP, revealed a close similarity in the topographical distribution of [H-3][Pro9]-SP and [H-3]SP binding sites. Biochemical, pharmacological, and autoradiographic data obtained with [H-3][Pro9]-SP did not provide any evidence for the existence of subtypes of NK-1 binding sites. [Pro9]-SP had neither agonist nor antagonist properties on NK-2 and NK-3 receptors. Indeed, it did not stimulate phosphoinositide turnover on the hamster urinary bladder (NK-2 assay) and was devoid of activity on the contraction of the rabbit pulmonary artery (NK-2 assay) and of the rat portal vein (NK-3 assay). As a result of its high selectivity, [Pro9]-SP thus appears an excellent tool for investigating the functional properties of NK-1 receptors.
引用
收藏
页码:879 / 889
页数:11
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