[H-3] R-TERAZOSIN BINDS SELECTIVELY TO ALPHA(1)-ADRENOCEPTORS OVER ALPHA(1)-ADRENOCEPTORS - COMPARISON WITH RACEMIC [H-3] TERAZOSIN AND [H-3] PRAZOSIN

Most tissue sources for adrenoceptors contain a mixed population of al pha(1)- and/or alpha(2)-adrenoceptor subtypes; thus studies using non- specific radioligands are complicated by receptor heterogeneity. The e xamination of alpha(1)-adrenoceptor radioligand binding by radiolabele d terazosin and its enantiomers was simplified by using mouse fibrobla st cells, which are thymidine kinase mutant (LTK-), transfected with c loned alpha(1a)(-), alpha(1b), alpha(1d)-adrenoceptor subtypes. [H-3]T erazosin and its enantiomers were equipotent at the alpha(1b)-adrenoce ptor. [H-3]R-Terazosin was significantly less potent than [H-3]terazos in and [H-3]S-terazosin at the alpha(1a)- and the alpha(1d)-adrenocept ors. Using tissue derived alpha-adrenoceptors prepared in cold 25 mM g lycyl-glycine buffer, [H-3]prazosin, [H-3]terazosin and [H-3]S-terazbs in bound to two sites in the rat neonatal lung preparation consistent with the presence of both alpha(1)- and alpha(2B)-adrenoceptors. The r elative binding potencies of these radioligands at these two sites cor related with low affinity binding to the alpha(2B)-adrenoceptor and hi gh affinity binding to an alpha(1)-adrenoceptor. [H-3]R-Terazosin, on the other hand, bound to a single site in the rat neonatal lung membra ne preparation, most likely an alpha 1-adrenoceptor. Thus, [H-3]R-tera zosin may be useful as a selective alpha(1)-adrenoceptor radioligand f or establishing the functional role of adrenoceptors in tissues expres sing multiple subtypes.