AUTORADIOGRAPHIC LOCALIZATION OF [H-3] NICARDIPINE BINDING-SITES IN THE HUMAN RENAL-ARTERY

In the present study the pharmacological profile and the anatomical di stribution of dihydropyridine-type Ca2+ channels were analyzed in sect ions of the human renal artery by the use of combined radioligand bind ing and autoradiographic techniques with [H-3]nicardipine as a ligand. The binding of [H-3]nicardipine to sections of renal artery was time- , temperature- and concentration-dependent belonging, at least in the range of radioligand concentrations used, to a single class of high-af finity binding sites. The dissociation constant (K(D)) value was 0.3 n M and the maximum density of binding sites (B(max)) was 248 +/- 16 fmo l/mg tissue. The pharmacological profile of [H-3]nicardipine binding t o sections of human renal artery was consistent with the labeling of d ihydropyridine-type Ca2+ channels. In fact, dihydropyridine derivative s were the most powerful competitors of [H-3]nicardipine binding, wher eas phenylalkilamine, benzothiazepine or non-selective channel modulat ors were weak or ineffective competitors. Light microscope autoradiogr aphy revealed the highest density of [H-3]nicardipine binding sites in the tunica media of the renal artery, probably within smooth muscle c ells. A smaller accumulation of the radioligand occurred in the tunica adventitia, whereas the tunica intima did not show specific binding. These results indicate that light microscope autoradiography technique s associated with radioligand binding may represent a useful tool for analyzing the localization of receptors or targets of drug action with in the arterial wall.