Endothelin-induced endocytosis of cell surface ETA receptors. Endothelin remains intact and bound to the ETA receptor.

We demonstrate unusual features of the intracellular processing of endothelin-1 (ET-1) and its receptor ETA, the receptor subtype that mediates contraction of vascular smooth muscle cells. First, we show that in stably transfected CHO cells expressing ETA, binding of an ET-1 ligand induces rapid endocytosis of cell surface ETA. Receptor endocytosis was measured both by immunofluorescence and by radioiodinated antibodies specific for ETA. Second, we demonstrate that ET-1 remains intact for up to 2 h after endocytosis and, as judged by co-immunoprecipitation, internalized 125I-ET-1 remains bound to ETA receptors. We hypothesize that internalized ET-1, bound to ETA receptors, continues to activate a signal-transducing G protein, thus accounting for the prolonged period of contraction induced in smooth muscle cells by a single administration of ET-1.