EXPRESSION OF ALPHA(1)-ADRENOCEPTOR SUBTYPES IN RAT-TISSUES - IMPLICATIONS FOR ALPHA(1)-ADRENOCEPTOR CLASSIFICATION

We report here the mapping of the mRNA distribution of three different alpha(1)-adrenoceptor subtypes (alpha(1b), alpha(1c) and alpha(1d)) i n various rat tissues. cDNA fragments covering the region from the fif th to seventh putative transmembrane spanning domains of these three a lpha(1)-adrenoceptor subtypes were generated from rat hippocampus usin g reverse transcription coupled to polymerase chain reaction (PCR). Th ese three alpha(1)-adrenoceptor cloned cDNA fragments were then used a s subtype-selective cDNA probes in Northern blot analysis. Of the thre e specific DNA probes only the rat alpha(1b)-adrenoceptor probe hybrid ized to mRNA of rat liver. The rat alpha(1c)-adrenoceptor probe hybrid ized to a mRNA species of 3.7 kb in tissues that have been reported to contain the classical pharmacologically-defined alpha(1A)-adrenocepto r such as hippocampus, vas deferens, lung and salivary gland. Also, a major mRNA transcript of 2.7 kb was detected in hippocampus, vas defer ens and lung, using the rat alpha(1d)-adrenoceptor probe. In addition, pharmacological characterization of [H-3]prazosin binding to three st ably transfected mammalian cell-lines expressing one of the three alph a(1)-adrenoceptor subtypes cloned to date (namely, alpha(1b)- of the h amster smooth muscle DDT1-MF2 cell-line, the bovine brain alpha(1c) - and the rat cerebral cortical alpha(1d)-adrenoceptors) was performed. Of the three cloned alpha(1)-adrenoceptor subtypes the alpha(1c)-adren oceptor showed a similar pharmacological profile to that of the classi cal alpha(1A)-adrenoceptor of rat salivary gland. Our data on the phar macological profile and expression pattern of the alpha(1c)-adrenocept or indicate, in contrast to earlier claims (Schwinn et al., J. Biol. C hem. 265, 1990), that this subtype is in fact the classical pharmacolo gically-defined alpha(1A)-adrenoceptor subtype.