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Differential effects of antimycin A on endocytosis and exocytosis of transferrin also are observed for internalization and externalization of beta-adrenergic receptors

JF Liao and JP Perkins

Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.

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- induced endocytosis of the receptor, probably via clathrin-coated pits. Previously, we demonstrated that reduction of cellular ATP content with antimycin A completely blocked endocytosis of epidermal growth factor and translocation of beta-adrenergic receptors in 1321N1 astrocytoma cells. However, the effect of reduction in ATP content on endocytosis remains controversial. In the present report, we demonstrate that reduction of ATP content to a level < 5% of that in control cells is sufficient to prevent endocytosis of [125I]iodotransferrin and translocation of beta-adrenergic receptors. The further demonstration that reactions leading to the return of internalized transferrin or beta-adrenergic 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 and transferrin. The differential requirement for ATP of the two arms of diacytosis provides the basis for an explanation of the controversy regarding a requirement for ATP in endocytosis via clathrin-coated pits.

Volume 44, Issue 2, pp. 364-370, 08/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1993 by the American Society for Pharmacology and Experimental Therapeutics