DIFFERENCE IN THE FATE OF THE POTENT VASOCONSTRICTORS ANGIOTENSIN-II AND ENDOTHELIN INTERNALIZED VIA THEIR RECEPTOR-MEDIATED ENDOCYTOSIS

Receptor-mediated endocytosis of the potent vasoconstrictors, angiotensin II (AII) and endothelin (ET), was studied in Chinese hamster ovary (CHO) cells stably expressing the recombinant AII receptor type 1A (AT(1A)) and ET receptor type A (ET(A)), respectively In CHO cells equilibrated with I-125-AII and I-125-ET-1 at 4 degrees C, specifically bound radioligands were both rapidly internalized temperature-dependently with respective half times for AII and ET of 1.5 and 2.5 min at 37 degrees C, 2 and 5 min at 30 degrees C, 3 and 7 min at 25 degrees C, and 8 and 24 min at 18 degrees C. However, the fate of internalized ligands was strikingly different for the two peptides. Most I-125-AII was degraded and recycled back into the medium, whereas I-125-ET-1 was neither degraded nor returned to the medium during the first 60 min after its binding to the receptor. These data suggest that the different fates of the internalized ligands might account for several unique ET-induced actions contrasting with AII-elicited actions in the same target cells.