Interactions between endothelin and the dihydropyridine-type calcium antagonist nicardipine in the human renal artery: a radioligand and autoradiographic study.
The interactions between dihydropyridine Ca2+ channels and endothelin were analysed using combined radioligand binding and autoradiographic techniques. 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. 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. Endothelin-1, from a concentration of 1 pM l-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. 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.
Amenta
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Sezione di Anatomia Umana, Università di Camerino, Italy.
Rossodivita
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Ferrante
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D000368:Aged; D001345:Autoradiography; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007536:Isomerism; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D009529:Nicardipine / Q000493:pharmacokinetics / Q000494:pharmacology*; D011869:Radioligand Assay; D012077:Renal Artery / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism
D015220:Calcium Channels; D016232:Endothelins; D009529:Nicardipine