期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1983
卷号：80
期号：8
页码：2102-2106
DOI：10.1073/pnas.80.8.2102
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：An azide analog, 2-[4-(4-azidobenzoyl)piperazin-1-yl]-4-amino-6, 7-dimethoxyquinazoline (CP59,430), of the highly selective alpha 1-adrenergic receptor antagonist prazosin was synthesized and its effects on rat hepatic membrane and affinity-purified alpha 1-adrenergic receptor preparations were examined. CP59,430 behaved as a competitive antagonist before photolysis. When the membrane or purified preparations pretreated with CP59,430 were irradiated with UV light, CP59,430 behaved as a noncompetitive antagonist. Labeling of membrane alpha 1-adrenergic receptors was irreversible; repeated dialysis or washing could not reverse the photolysis-induced inactivation by CP59,430, whereas dialysis completely reversed the antagonism by the same concentration of the label prior to photolysis. Additionally, photolabeling of purified receptors was resistant to Sephadex G-50 chromatography, whereas in the absence of photolysis the same concentration of CP59,430 or prazosin (10 microM) could be readily removed by this procedure. CP59,430 appears to label specifically only alpha 1-adrenergic receptors because prazosin protected the membrane and purified receptors from photolysis-induced inactivation by CP59,430. Furthermore, specific [3H]dihydroalprenolol and [3H]yohimbine binding to membrane beta- and alpha 2-adrenergic receptors, respectively, was unchanged by CP59,430 at 1 microM, a concentration that decreased specific [3H]prazosin binding to alpha 1-adrenergic receptors by 72%. In additional studies, the photolysis-induced receptor inactivation by CP59,430 remained unchanged in the presence of the scavenger p-aminobenzoic acid. It is likely, therefore, that receptor labeling by CP59,430 occurs via a true photoaffinity mechanism. CP59,430, which specifically and irreversibly labels the alpha 1-adrenergic receptor after photolysis, should thus be uniquely valuable for the molecular characterization of this receptor.
