Coupling efficiency of brain beta-adrenergic receptors to G(s) protein in suicide, alcoholism and control subjects

Abnormal beta-adrenergic receptor (beta AR) density in the brains of suicid e victims has been reported, although results of studies are inconsistent. Ethanol modifies beta AR-mediated signal transduction. Moreover abnormal be ta AR function has been implicated in alcoholism. beta AR antagonists, whic h were used as ligands in previous beta AR binding studies, also bind to 5- HT1B/1D beta receptors; hence, their estimates of beta AR density are confo unded by binding to 5-HT1B/1D beta receptors. More importantly, previous st udies did not examine beta AR agonist affinity or coupling efficiency to G( s) protein. We investigated agonist affinity and coupling efficiency of bet a AR to G(s) protein in the brains of ten suicide victims, six subjects wit h alcoholism, and eight controls. There were no differences in beta AR dens ity in either the frontal cortex or hippocampus of suicide victims or alcoh olic subjects compared to controls, Preliminary results indicate beta AR su percoupling in suicide victims in both brain regions and uncoupling in alco holic subjects in the frontal cortex. These results are discussed in view o f the existing literature on the role of beta AR in suicide and alcoholism and the mechanism of action of antidepressants.