Probing of β-adrenergic receptors by novel fluorescent β-adrenergic blockers

Publisher Website
Google Scholar
Abstract
The synthesis of two high-affinity fluorescent β-adrenergic blockers is described: dl-N 1 -[2-hydroxy-3-(1-naphthyloxy)propyl]- N 2 -(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 [ 125 I]-iodohydroxybenzylpindolol to these β-adrenergic receptors. The two fluorescent β-adrenergic blockers 9-AAP and DAPN probe specifically β-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 β-adrenergic receptors in vivo . The stereospecific displacement of 9-AAP from the β-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 β-receptors in vitro and in vivo is discussed.