Agonist-specific effects of monovalent and divalent cations on adenylate cyclase-coupled alpha adrenergic receptors in rabbit platelets
Tsai, B.S.; Lefkowitz, R.J.
Molecular Pharmacology 14(4): 540-548
1978
ISSN/ISBN: 0026-895X PMID: 210368 Document Number: 129158
The .alpha. adrenergic receptors of rabbit platelets can be identified by using /mg, and the Kd was 2.26 .+-. 0.48 nM. The specificity of the binding sites for receptor agonists and antagonists is consistent with that of an .alpha. adrenergic response in inhibiting prostaglandin E1-stimulated adenylate cyclase in the same lysate preparation and is thus in agreement with the classical definition of .alpha.-adrenergic receptors in mediating physiological responses. Divalent cations such as Mg and Mn and monovalent cations such as Na markedly influence the binding affinity of agonists but have little or no effect on the binding of antagonists. Ca produces no change in binding. Neither Mg nor Na alters the number of receptor sites. Mg (1.25 mM) increases the binding affinity of (.sbd.)-epinephrine by a factor of 4, while NaCl (100 mM) strikingly decreases the binding affinity of agonists (more than 10-fold). The effect of NaCl on agonists is apparent with concentrations as low as 10 mM, and shows a dose-dependent response. LiCl and KCl are only 44% and 19% as effective, respectively, as NaCl. The magnitude of the shift in binding affinity of .alpha.-adrenergic agents produced by NaCl is directly related to the intrinsic activity of those agents for inhibition of prostaglandin E1-stimulated adenylate cyclase. Physiological concentrations of MgCl and NaCl may selectively regulate the binding affinity of agonists.