Agonist-specific effects of guanine nucleotides on alpha-adrenergic receptors in human platelets
Tsai, B.S.; Lefkowitz, R.J.
Molecular Pharmacology 16(1): 61-68
1979
ISSN/ISBN: 0026-895X PMID: 39249 Document Number: 139183
The effect of GTP on the binding affinity of .alpha.-adrenergic receptors for .alpha.-adrenergic agents was studied in human platelet lysates using direct ligand binding methods with E1-stimulated adenylate cyclase. The effect of GTP appears to depend on the concurrent presence of Mg2+. In the absence of Mg2+, GTP caused only a slight decrease in the agonist binding affinity. When Mg2+ was present without GTP, the binding affinity of the agonist (-)epinephrine was increased 5-fold. GTP in the presence of Mg2+ induces a state of diminished affinity of the receptor for the agonist which is lower than that induced by the nucleotide in the absence of MgCl2. The relationship between GTP and MgCl2 in the regulation of platelet .alpha.-adrenergic receptors which are inhibitory to adenylate cyclase activity appears to be analogous to their role in regulating .beta.-adrenergic receptors which are stimulatory for the enzyme in other tissues.