Coupling efficiency of brain β-adrenergic receptors to Gs protein in suicide, alcoholism and control subjects

Abstract

Abnormal β-adrenergic receptor (βAR) density in the brains of suicide victims has been reported, although results of studies are inconsistent. Ethanol modifies βAR-mediated signal transduction. Moreover abnormal βAR function has been implicated in alcoholism. βAR antagonists, which were used as ligands in previous βAR binding studies, also bind to 5-HT_1B/1Dβ receptors; hence, their estimates of βAR density are confounded by binding to 5-HT_1B/1Dβ receptors. More importantly, previous studies did not examine βAR agonist affinity or coupling efficiency to G_s protein. We investigated agonist affinity and coupling efficiency of βAR to G_s protein in the brains of ten suicide victims, six subjects with alcoholism, and eight controls. There were no differences in βAR density in either the frontal cortex or hippocampus of suicide victims or alcoholic subjects compared to controls. Preliminary results indicate βAR supercoupling in suicide victims in both brain regions and uncoupling in alcoholic subjects in the frontal cortex. These results are discussed in view of the existing literature on the role of βAR in suicide and alcoholism and the mechanism of action of antidepressants.