The α1-adrenoceptor is inactivated by alterations in membrane phospholipids

Abstract The influence of the membrane environment on the α 1 -adrenoceptor has been investigated by examining the effect of phospholipase digestion on the binding of [ 3 H]prazosin to aortic and hepatic membranes. Membrane digestion by phospholipase A 2 and phospholipase C was found to markedly reduce prazosin binding to the α 1 -adrenoceptor whereas phospholipase D had comparatively little effect. In addition, there were differences between membrane preparations since the aortic α 1 -adrenoceptor was less sensitive to phospholipase A 2 and phospholipase C than the hepatic receptor. The results support a major role for hydrophobic groups and the negatively charged, hydrophilic phosphate moiety of phospholipids in the interaction between prazosin and the α 1 -adrenoceptor.