TY - JOUR T1 - Independent Desensitization of β-Adrenergic Receptor-Regulated Magnesium Transport and Cyclic AMP Accumulation JF - Molecular Pharmacology JO - Mol Pharmacol SP - 379 LP - 383 VL - 18 IS - 3 AU - JOSEPH J. ERDOS AU - MICHAEL E. MAGUIRE Y1 - 1980/11/01 UR - http://molpharm.aspetjournals.org/content/18/3/379.abstract N2 - We have previously shown that β-adrenergic inhibition of Mg2+ transport in cultured S49 lymphoma cells is not mediated by cyclic AMP (Maguire, M. E., and J. J. Erdos. J. Biol. Chem. 255: 1030-1035 (1980). We now report that the rate of Mg2+ but not Ca2+ influx is decreased immediately upon the addition of (-)-isoproterenol and remains decreased at a constant rate for approximately 25 min in both wild-type and kinase- clones in the continued presence of agonist. The rate of Mg2+ influx gradually increases between 30 and 60 min, and complete desensitization to (-)-isoproterenol occurs after about 60-70 min. In contrast, cyclic AMP accumulation after the addition of (-)-isoproterenol peaks within 3 min in wild-type S49 cells. The calculated rate of cyclic AMP synthesis in intact wild-type cells falls to zero after 3 min of incubation even though biologically active agonist is still present at a high concentration. This acute desensitization is not due to activation of phosphodiesterase since identical time courses are obtained either in wild-type cells with a phosphodiesterase inhibitor or in kinase- S49 cells which have little or no detectable phosphodiesterase activity. These results indicate that β-adrenergic stimulation of cyclic AMP accumulation and therefore adenylate cyclase desensitizes independently of β-adrenergic inhibition of Mg2+ influx. Thus, not only is inhibition of Mg2+ transport by β-adrenergic receptor occupancy not mediated by cyclic AMP, but this receptor-modulated transport event appears to be regulated independently of adenylate cyclase. ACKNOWLEDGMENTS We thank Paula L. Jacobs for excellent technical assistance and Drs. John J. Mieyal and Stephen A. Rudolph for their reading of the manuscript. ER -