Beta-adrenergic desensitization reduces the sensitivity of adenylate cyclase for magnesium in permeabilized lymphocytes.
Magnesium modulates hormone-sensitive adenylate cyclase activation. In the present studies, we have examined the magnesium requirement of beta-adrenergic-stimulated adenylate cyclase activity in permeabilized human lymphocytes. Following isoproterenol pretreatment, under conditions that lead to homologous beta-adrenergic desensitization, the EC50 of magnesium for beta-adrenergic-stimulated adenylate cyclase activity was significantly increased [control; 1.99 (+0.81/-0.57) mM; desensitized; 3.82 (+0.31/-0.29) mM]. Further, when assays were performed at high Mg2+ concentrations following agonist pretreatment, we detected only small and inconsistant reductions in beta-adrenergic-stimulated adenylate cyclase activity and in beta-adrenergic cAMP-dependent protein kinase activity. In contrast, the detection of agonist-induced beta-adrenergic receptor sequestration and alterations in receptor affinity for agonists was not qualitatively affected by changes in magnesium concentrations. The data demonstrate that the functional consequences of beta-adrenergic desensitization may be obscured at high magnesium concentrations. Furthermore, in this system desensitization may be viewed as a beta-receptor-specific reduction in magnesium sensitivity.
Feldman
R D
RD
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
D000262:Adenylyl Cyclases / Q000032:analysis*; D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008214:Lymphocytes / Q000201:enzymology*; D008274:Magnesium / Q000378:metabolism / Q000494:pharmacology*; D011412:Propanolamines / Q000494:pharmacology; D011494:Protein Kinases / Q000032:analysis; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D011494:Protein Kinases; D000262:Adenylyl Cyclases; D008274:Magnesium; D007545:Isoproterenol; C033394:CGP 12177