MATERNAL ETHANOL-CONSUMPTION - EFFECTS ON G-PROTEINS AND 2ND MESSENGERS IN BRAIN-REGIONS OF OFFSPRING

Previous work in this and other laboratories has demonstrated that in utero ethanol exposure adversely affects the development of the seroto nergic, dopaminergic, cholinergic, and other neurotransmitter systems. In several of these systems, receptor number is significantly altered . To determine whether the altered number of two G protein-linked rece ptors is reflected in changes in cell function, we examined dopamine s timulated adenylate cyclase in the striatum and cortex and carbachol s timulated phosphoinositide (PI) hydrolysis in the cortex. Serotonin-st imulated cortical PI hydrolysis was assessed for comparison. We also s tudied G proteins that link adenylate cyclase and other second messeng er systems to their receptors. The G proteins that were analyzed inclu de the alpha-subunits for G(s), G(0), G(i1), G(i2), and G(i3) G protei ns were analyzed in the cortex and cortical regions, as well as in the brain stem. The results of these experiments demonstrated that dopami ne stimulated adenylate cyclase activity was comparable in the striatu m of 5- and 19-day offspring of control and ethanol fed rats and in th e motor cortex of Ig day offspring. We also found that carbachol- and serotonin-stimulated hydrolysis of cortical phosphoinositides was unch anged in ethanol exposed offspring on gestational day 19, and on postn atal days 5 and 19. G protein content was examined by Western blot ana lysis, using antibodies directed against the alpha-subunits of G(s), G (0), and the G(i1)/G(i2) and G(i3)/G(0) combinations. These investigat ions indicated that, with two minor exceptions (similar to 10% change in the proteins detected by antibodies against the alpha-subunits of t he G(i1)/G(i2) and G(i3)/G(0) combinations), there were no significant differences in the content of any of the G proteins analyzed.