Serotonin receptor binding sites affected differentially by guanine nucleotides

Guanosine triphosphate (GTP) and diphosphate (GDP) decrease the binding of the agonist [³H]serotonin (5-HT) to serotonin receptors in mammalian brain membranes. Binding of the antagonist [³H]spiroperidol is not affected by guanine nucleotides while the mixed agonist-antagonist [³H]lysergic acid diethylamide ([³H]LSD) is affected in an intermediate manner. GTP lowers the apparent affinity of [³H]5-HT for its receptors without changing the number of binding sites. Both the association and dissociation rates of [³H]5-HT are increased by GTP. The potency of 5-HT agonists in competing for [³H]5-HT but not [³H]LSD or [³H]spiroperidol binding sites is decreased by GTP. Competition by partial agonists and antagonists for [³H]5-HT binding sites is not affected by GTP.