RT Journal Article SR Electronic T1 Rat cardiac muscarinic receptors. I. Effects of guanine nucleotides on high- and low-affinity binding sites. JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 581 OP 588 VO 21 IS 3 A1 M Waelbroeck A1 P Robberecht A1 P Chatelain A1 J Christophe YR 1982 UL http://molpharm.aspetjournals.org/content/21/3/581.abstract AB The binding properties of muscarinic cholinergic binding sites were investigated in rat cardiac membranes, using the labeled agonist [3H] oxotremorine-M ([3H]Oxo-M) and the labeled antagonist L-[benzilic-4,4'-3H]quinuclidinyl benzilate (L-[3H]QNB). The binding of both tracers was inhibited stereospecifically by dexetimide and levitimide. [3H]Oxo-M labeled only high-affinity agonist binding sites, whereas L-[3H]QNB bound to high- and low-affinity agonist binding sites with equal affinity. Agonists were unable to induce "negative cooperativity" interactions by increasing the dissociation of labeled agonist or antagonist. Guanine nucleotides decreased markedly the affinity of high- and low-affinity binding sites for agonists, without affecting their affinity for antagonists. In the presence of a maximally effective concentration of GTP, all muscarinic receptors showed the same low affinity for agonists. Among these agonists, carbamylcholine and oxotremorine (but not pilocarpine) displayed a lower affinity for both classes of binding sites in the presence of GTP.