Study of the Mechanism of Hormone Induced Desensitization and Internalization of Beta-Adrenergic Receptors
The hormone epinephrine exerts its effects by binding to specific plasmamembrane receptors. The receptors interact with the membrane-bound enzyme complex of adenylate cyclase which catalyzes the formation of adenosine-3′, 5′-cyclic monophosphate (cyclic AMP). Cultured S49 mouse lymphoma cells become refractory or desensitized to hormone after stimulation for relatively short periods (20–30 minutes), i.e. no further cyclic AMP is synthetized when the cells are subsequently exposed to a second hormone dose. Desensiti-zation during the first 30 minutes after hormone addition to intact cells is characterized by a rapid decline in the rate of cyclic AMP production (Figure 1) and uncoupling of cell surface receptors followed by internalization of the receptors (1,2,3). In S49 cells, at 37°C, 50–60 % of the receptors originally present on the plasma membrane are internalized 2–4 minutes after administration of agonist (e.g. 1 micromolar isoproterenol). About 40 % of the receptors, however, remain on the cell surface, even after stimulation with isoproterenol for several hours (2).
KeywordsAdenylate Cyclase Adenylate Cyclase System Noncatalytic Site Phenylarsine Oxide Coleus Forskohlii
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