Down-regulation of Endothelin Binding Sites in Rat Vascular Smooth Muscle Cells

In cultured rat aortic smooth muscle cells, [125I]en-dothelin (ET-1) bound to an apparent single class of high affinity recognition sites with a dissociation constant of 1.84 ± 0.29 nmol/L and a maximum binding of 62 ± 10.5 fmol/106 cells. The binding was not affected by calcium antagonists or vasoac-tive substances, including angiotensin II, arginine vasopressin, atrial natriuretic factor and brady-kinin. Exposure of the cells to ET-1 (0.01 nmol/L to 10 nmol/L) resulted in an apparent dose-dependent reduction of the number of endothelin binding sites with no significant modification of its binding affinity. The time course of the down-regulation of ET-1 binding sites showed that this effect was present after 30 min incubation and persisted after 18 h. This indicates that down-regulation of ET-1 binding sites can modulate the activity of ET-1 and suggests a rapid internalization of ET-1 in vascular cells. Am J Hypertens 1990;3:310-312