RT Journal Article
SR Electronic
T1 Beta-adrenergic desensitization reduces the sensitivity of adenylate cyclase for magnesium in permeabilized lymphocytes.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 304
OP 310
VO 35
IS 3
A1 R D Feldman
YR 1989
UL http://molpharm.aspetjournals.org/content/35/3/304.abstract
AB 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.