Autoradiographic localization of [3H]nicardipine binding sites in the human renal artery.

In the present study the pharmacological profile and the anatomical distribution of dihydropyridine-type Ca2+ channels were analyzed in sections of the human renal artery by the use of combined radioligand binding and autoradiographic techniques with [3H]nicardipine as a ligand. The binding of [3H]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-affinity binding sites. The dissociation constant (KD) value was 0.3 nM and the maximum density of binding sites (Bmax) was 248 +/- 16 fmol/mg tissue. The pharmacological profile of [3H]nicardipine binding to sections of human renal artery was consistent with the labeling of dihydropyridine-type Ca2+ channels. In fact, dihydropyridine derivatives were the most powerful competitors of [3H]nicardipine binding, whereas phenylalkilamine, benzothiazepine or non-selective channel modulators were weak or ineffective competitors. Light microscope autoradiography revealed the highest density of [3H]nicardipine binding sites in the tunica media of the renal artery, probably within smooth muscle cells. 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 techniques associated with radioligand binding may represent a useful tool for analyzing the localization of receptors or targets of drug action within the arterial wall.