Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, the actions of which are mediated through interaction with specific ET receptors. Functional evidence has shown that the constrictor effect of ET may require extracellular Ca2+. Ca2+ antagonists of the dihydropyridine family attenuate the vasoconstriction caused by ET. However, the basis of the interactions between ET and dihydropyridine agents are not well understood. Our study was designed to assess whether different concentrations of ET-1 or ET-3 have any effect on [3H]nicardipine binding to sections of human renal artery. [3H]Nicardipine was specifically bound to sections of the human renal artery. Binding sites, which were located primarily over smooth muscle of the tunica media, showed the pharmacologic profile typical of a dihydropyridine Ca2+ channel. Increasing concentrations of ET-1, but not of ET-3, competed dose-dependently with [3H]nicardipine binding. A 1-nM concentration of ET-1 lessened specific [3H]nicardipine binding by approximately 80%. These results suggest the occurrence of an interaction in the human renal artery between dihydropyridine Ca2+ channels and ET-1. This interaction probably accounts for the inhibition of the ET-1-mediated vasoconstriction elicited by nicardipine.
Endothelin-1 displaces [3H]nicardipine binding in sections of human renal artery.
AMENTA, Francesco;
1993-01-01
Abstract
Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, the actions of which are mediated through interaction with specific ET receptors. Functional evidence has shown that the constrictor effect of ET may require extracellular Ca2+. Ca2+ antagonists of the dihydropyridine family attenuate the vasoconstriction caused by ET. However, the basis of the interactions between ET and dihydropyridine agents are not well understood. Our study was designed to assess whether different concentrations of ET-1 or ET-3 have any effect on [3H]nicardipine binding to sections of human renal artery. [3H]Nicardipine was specifically bound to sections of the human renal artery. Binding sites, which were located primarily over smooth muscle of the tunica media, showed the pharmacologic profile typical of a dihydropyridine Ca2+ channel. Increasing concentrations of ET-1, but not of ET-3, competed dose-dependently with [3H]nicardipine binding. A 1-nM concentration of ET-1 lessened specific [3H]nicardipine binding by approximately 80%. These results suggest the occurrence of an interaction in the human renal artery between dihydropyridine Ca2+ channels and ET-1. This interaction probably accounts for the inhibition of the ET-1-mediated vasoconstriction elicited by nicardipine.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
