Related Experiment Video
Updated: Aug 14, 2026

Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications
Published on: January 27, 2014
Beta-adrenergic desensitization reduces the sensitivity of adenylate cyclase for magnesium in permeabilized
1Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Abstract:
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.
More Related Videos
Related Concept Videos
GPCR Desensitization
GPCRs Regulate Adenylyl Cylase Activity
Two...
Desensitization and Tachyphylaxis
Several...
Adrenergic Receptors (Adrenoceptors): Classification
α-Adrenoceptors
α-Adrenoceptors are classified into two main subtypes: α1 and α2. The α1 adrenoceptors, which are found on postsynaptic...
Adrenergic Receptors: ɑ Subtype
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase C—inositol-1,4,5-trisphosphate...
Adrenergic Receptors: β Subtype
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors have equal affinities for...

