Effect of Mg²⁺ on guanine nucleotide sensitivity of ligand binding to serotonin_1A receptors from bovine hippocampus

Abstract

The serotonin_1A (5-HT_1A) receptor is an important member of the superfamily of seven transmembrane domain G-protein coupled receptors (GPCRs). We report here that guanine nucleotide sensitivity of agonist binding to hippocampal 5-HT_1A receptors is dependent on the concentration of Mg²⁺. Our results show that agonist binding to 5-HT_1A receptors is relatively insensitive to guanine nucleotides in the absence of Mg²⁺. In contrast to this, the specific antagonist binding is insensitive to guanine nucleotides, even in the presence of Mg²⁺. These results point out the requirement of an optimal concentration of Mg²⁺ which could be used in assays toward determining guanine nucleotide sensitivity of ligand binding to GPCRs such as the 5-HT_1A receptor. Our results provide novel insight into the requirement and concentration dependence of Mg²⁺ in relation to guanine nucleotide sensitivity for the 5-HT_1A receptor in particular, and GPCRs in general.