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：1977
卷号：74
期号：12
页码：5290-5294
DOI：10.1073/pnas.74.12.5290
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The synthesis of two high-affinity fluorescent {beta}-adrenergic blockers is described: dl-N1-[2-hydroxy-3-(1-naphthyloxy)propyl]-N2-(9-acridyl)-1,2-propanediamine (9-aminoacridylpropanolol, 9-AAP) and dl-N-[2-hydroxy-3-(1-naphthyloxy)propyl]-N'-dansylethylenediamine (dansyl analogue of propranolol, DAPN). Both 9-AAP and DAPN inhibit competitively the l-epinephrine-dependent adenylate cyclase activity [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1 ] in turkey erythrocyte membranes without affecting the fluoride-stimulated adenylate cyclase activity. Similarly, 9-AAP and DAPN inhibit in a competitive manner the binding of [125I]-iodohydroxybenzylpindolol to these {beta}-adrenergic receptors. The two fluorescent {beta}-adrenergic blockers 9-AAP and DAPN probe specifically {beta}-adrenergic receptors in the central nervous system as well as in other organs when injected into rats. The fluorescence pattern can be monitored by fluorescence microscopy performed on cryostat slices of these organs. The appearance of the characteristic fluorescence pattern can be blocked in a stereospecific fashion by a prior injection of l-propranolol and not by a prior injection of d-propranolol. These compounds therefore offer a powerful means to map {beta}-adrenergic receptors in vivo. The stereospecific displacement of 9-AAP from the {beta}-adrenergic receptors of turkey erythrocyte membranes by l-propranolol and by l-epinephrine can be detected in vitro using front-face fluorescence. The potential use of these compounds to probe {beta}-receptors in vitro and in vivo is discussed.
关键词：membrane adenylate cyclase ; fluorescence microscopy ; 9-aminoacridylpropranolol ; dansyl analog of propranolol
