Interactions between endothelin and the dihydropyridine-type calcium antagonist nicardipine in the human renal artery: a radioligand and autoradiographic study

Autor: Francesco Amenta, Fabio Ferrante, I. Rossodivita
Rok vydání: 1994
Předmět:
Zdroj: Journal of Autonomic Pharmacology. 14:129-136
ISSN: 1365-2680
0144-1795
DOI: 10.1111/j.1474-8673.1994.tb00597.x
Popis: 1 The interactions between dihydropyridine Ca2+ channels and endothelin were analysed using combined radioligand binding and autoradiographic techniques. 2 Endothelin is a potent constrictor peptide of arterial smooth muscle. Endothelin-induced vasoconstriction is attenuated by dihydropyridine-type Ca2+ antagonists such as nicardipine. However, the molecular mechanisms of this effect are not yet understood. 3 Sections of the human renal artery bound [3H]-nicardipine in a manner consistent with the labelling of dihydropyridine-type Ca2+ channels. The highest density of [3H]-nicardipine binding sites occurred within the tunica media of the renal artery, probably over smooth muscle. A lower density of [3H]-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 [3H]-nicardipine binding as a function of concentration. A 10 nm endothelin concentration reduced [3H]-nicardipine binding by about 85%. The isoform, endothelin-3, had little effect on [3H]-nicardipine binding. 5 The above findings suggest the occurrence of an interaction, probably at the receptor level, between [3H]-nicardipine binding and endothelin-1. This interaction probably accounts for the attenuation of endothelin-1-elicited vasoconstriction induced by nicardipine.
Databáze: OpenAIRE
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