INTERACTIONS BETWEEN ENDOTHELIN AND THE DIHYDROPYRIDINE-TYPE CALCIUM-ANTAGONIST NICARDIPINE IN THE HUMAN RENAL-ARTERY - A RADIOLIGAND AND AUTORADIOGRAPHIC STUDY

1 The interactions between dihydropyridine Ca2+ channels and endotheli n were analysed using combined radioligand binding and autoradiographi c techniques. 2 Endothelin is a potent constrictor peptide of arterial smooth muscle. Endothelin-induced vasoconstriction is attenuated by d ihydropyridine-type Ca2+ antagonists such as nicardipine. However, the molecular mechanisms of this effect are not yet understood. 3 Section s of the human renal artery bound H-3-nicardipine in a manner consis tent with the labelling of dihydropyridine-type Ca2+ channels. The hig hest density of H-3-nicardipine binding sites occurred within the tu nica media of the renal artery, probably over smooth muscle. A lower d ensity of H-3-nicardipine binding sites was noticeable in the tunica adventitia, whereas no specific binding occurred in the tunica intima . 4 Endothelin-1, from a concentration of 1 pm 1(-1), reduced H-3-ni cardipine binding as a function of concentration. A 10 nM endothelin c oncentration reduced H-3-nicardipine binding by about 85%. The isofo rm, endothelin-3, had little effect on H-3-nicardipine binding. 5 Th e above findings suggest the occurrence of an interaction, probably at the receptor level, between H-3-nicardipine binding and endothelin- 1. This interaction probably accounts for the attenuation of endotheli n-1-elicited vasoconstriction induced by nicardipine.