Effects of some membrane perturbers on alpha 1-adrenergic receptor binding

The ability of membrane perturbing drugs to inhibit the specific binding of [3H]/B4101 (2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane) to the alpha 1-receptor of beef cortical membranes was determined. Except for quinidine and phenytoin, the IC50 for inhibition of specific [3H]WB4101 binding to the alpha 1-receptor correlated with the membrane/buffer partition coefficient of the drug. Almost all of the drugs inhibited specific ligand binding at concentrations approaching those reported necessary to stabilize membranes although both activities correlate well with reported membrane/buffer partition coefficients. The results suggest that specific receptor function can be modified by drug perturbation of the lipid microenvironment of the receptor macromolecule.