Feldman R D
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Mol Pharmacol. 1989 Mar;35(3):304-10.
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.
镁调节激素敏感的腺苷酸环化酶的激活。在本研究中，我们检测了通透化人淋巴细胞中β-肾上腺素能刺激的腺苷酸环化酶活性对镁的需求。在异丙肾上腺素预处理后，在导致同源β-肾上腺素能脱敏的条件下，β-肾上腺素能刺激的腺苷酸环化酶活性所需镁的半数有效浓度（EC50）显著增加[对照；1.99（+0.81/-0.57）mM；脱敏后；3.82（+0.31/-0.29）mM]。此外，当在激动剂预处理后于高镁离子浓度下进行测定时，我们仅检测到β-肾上腺素能刺激的腺苷酸环化酶活性以及β-肾上腺素能环磷酸腺苷依赖性蛋白激酶活性有微小且不一致的降低。相比之下，激动剂诱导的β-肾上腺素能受体隔离以及受体对激动剂亲和力的改变在性质上不受镁浓度变化的影响。数据表明，在高镁浓度下，β-肾上腺素能脱敏的功能后果可能被掩盖。此外，在该系统中，脱敏可被视为镁敏感性的β受体特异性降低。
