Altered CTX‐catalyzed and endogenous [32P]ADP‐ribosylation of stimulatory G protein αs isoforms in postmortem bipolar affective disorder temporal cortex

Reports of elevated Gs α subunit (αs) immunolabeling and cAMP‐mediated hyper‐functionality in autopsied cerebral cortical brain regions from bipolar affective disorder (BD) patients suggest signal transduction abnormalities occur in this disorder. Because covalent modification of αs can affect its turnover and levels, we determined whether CTX‐catalyzed and endogenous [32P] adenosine diphosphate (ADP)‐ribosylation of αs isoforms are altered in temporal and occipital cortical regions, which show elevated αs levels in BD as compared to nonpsychiatric subjects. Reduced CTX‐catalyzed [32P]ADP‐ribosylated αs‐S and endogenous [32P]ADP‐ribosylation of a 39‐kDa αs‐like protein were found in BD temporal cortex compared to controls. These findings suggest that clearance of these αs isoforms through ADP‐ribosylation may be decreased in BD temporal cortex. Although no differences were observed in mean levels of endogenous and CTX‐catalyzed [32P]ADP‐ribosylation of αs‐L in BD temporal cortex, αs‐L immunolabeling was elevated significantly and correlated inversely with the degree of endogenous [32P]ADP‐ribosylation of this subunit. In addition, endogenous [32P]ADP‐ribosylation of an exogenous substrate, myelin basic protein, was similar in BD and comparison subject temporal cortex. Taken together, these observations suggest that elevations of αs in BD brain are more likely related to factors affecting the disposition or availability of αs to this posttranslational enzymatic modification. © 2003 Wiley‐Liss, Inc.