β-adrenoceptor studies. 6. Further investigations on the hybrid nature of the rat adipocyte β-adrenoceptor

Abstract

The nature of the rat adipocyte β-adrenoceptor was studied in further detail using a selected series of tolamol-type β-adrenoceptor antagonists. Isoprenaline antagonism by these compounds was evaluated on adipocytes, right atrium, left atrium and left hemidiaphragm of the rat. Adipocyte pA 2 values were corrected for binding to bovine serum albumin determined separately for each antagonist. A strong correlation between adipocyte and diaphragm pA 2 values was found with those antagonists which had an identical N-substituent but a different substitution pattern in the phenoxypropanolamine ring. This relationship was absent with those compounds which had the same 2-methylphenoxypropanolamine moiety but a different N-substituent. With the latter antagonists, however, adipocyte pA 2 values correlated significantly with the two cardiac pA 2 values. These results support the idea that the interaction site of the rat adipocyte β-adrenoceptor for the aromatic moiety of arylethanolamines and aryloxypropanolamines has β 2-characteristics whereas the alkanolamine side-chain interaction site has a β 1-nature. Finally, it was ascertained that the apparently dualistic ( β 1 and β 2) character of the rat adipocyte adrenoceptor is not due to the presence of both a β 1- and a β 2-receptor population on the fat cell plasma membrane.