Coupling efficiency of brain beta-adrenergic receptors to Gs protein in suicide, alcoholism and control subjects.
Abnormal beta-adrenergic receptor (betaAR) density in the brains of suicide victims has been reported, although results of studies are inconsistent. Ethanol modifies betaAR-mediated signal transduction. Moreover abnormal betaAR function has been implicated in alcoholism. BetaAR antagonists, which were used as ligands in previous betaAR binding studies, also bind to 5-HT1B/1Dbeta receptors; hence, their estimates of betaAR density are confounded by binding to 5-HT1B/1Dbeta receptors. More importantly, previous studies did not examine betaAR agonist affinity or coupling efficiency to Gs protein. We investigated agonist affinity and coupling efficiency of betaAR to Gs protein in the brains of ten suicide victims, six subjects with alcoholism, and eight controls. There were no differences in betaAR density in either the frontal cortex or hippocampus of suicide victims or alcoholic subjects compared to controls. Preliminary results indicate betaAR 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 betaAR in suicide and alcoholism and the mechanism of action of antidepressants.
Gurguis
G N
GN
Laboratory of Clinical Studies, DICBR, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD 20892-1256, USA. gurguis.george@dallas.va.gov
Turkka
J
J
Laruelle
M
M
Kleinman
J
J
Linnoila
M
M
D000319:Adrenergic beta-Antagonists / Q000032:analysis; D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000378:metabolism; D002540:Cerebral Cortex / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000032:analysis* / Q000378:metabolism; D006624:Hippocampus / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D020120:Iodocyanopindolol / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011943:Receptors, Adrenergic, beta / Q000032:analysis* / Q000378:metabolism; D013405:Suicide
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D019205:GTP-Binding Protein alpha Subunits, Gs