DIFFERENTIAL-EFFECTS OF ANTIMYCIN-A ON ENDOCYTOSIS AND EXOCYTOSIS OF TRANSFERRIN ALSO ARE OBSERVED FOR INTERNALIZATION AND EXTERNALIZATION OF BETA-ADRENERGIC RECEPTORS

In many cells catecholamines induce a translocation of beta-adrenergic receptors from the cell surface to intracellular vesicular sites. We have postulated that the translocation event is the result of ligand-i nduced endocytosis of the receptor, probably via clathrin-coated pits. Previously, we demonstrated that reduction of cellular ATP content wi th antimycin A completely blocked endocytosis of epidermal growth fact or and translocation of beta-adrenergic receptors in 1321N1 astrocytom a cells. However, the effect of reduction in ATP content on endocytosi s remains controversial. In the present report, we demonstrate that re duction of ATP content to a level <5% of that in control cells is suff icient to prevent endocytosis of [I-125]iodotransferrin and translocat ion of beta-adrenergic receptors. The further demonstration that react ions leading to the return of internalized transferrin or beta-adrener gic receptors to the cell surface are blocked after relatively modest reductions in ATP content provides further evidence of the similarity in the processes subserving diacytosis of beta-adrenergic receptors an d transferrin. The differential requirement for ATP of the two arms of diacytosis provides the basis for an explanation of the controversy r egarding a requirement for ATP in endocytosis via clathrin-coated pits .