Maternal Ethanol Consumption: Effects on G Proteins and Second Messengers in Brain Regions of Offspring

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Abstract
Previous work in this and other laboratories has demonstrated that in utero ethanol exposure adversely affects the development of the serotonergic, 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 receptors is reflected in changes in cell function, we examined dopamine-stimulated adenylate cyclase in the striatum and cortex and carbachol-stimulated phosphoinositide (PI) hydrolysis in the cortex. Serotonin-stimulated cortical PI hydrolysis was assessed for comparison. We also studied G proteins that link adenylate cyclase and other second messenger systems to their receptors. The G proteins that were analyzed include the α-subunits for Ga, Go, G11, G12, and G13. G proteins were analyzed in the cortex and cortical regions, as well as in the brain stem. The results of these experiments demonstrated that dopaminestimulated adenylate cyclase activity was comparable in the striatum of 5- and 19-day offspring of control and ethanol-fed rats and in the motor cortex of 19-day offspring. We also found that carbachol- and serotonin-stimulated hydrolysis of cortical phosphoinositides was unchanged in ethanol-exposed offspring on gestational day 19, and on postnatal days 5 and 19. G protein content was examined by Western blot analysis, using antibodies directed against the α-subunits of Ga, Go, and the G11/G12 and G13/Go combinations. These investigations indicated that, with two minor exceptions (∼10% change in the proteins detected by antibodies against the α-subunits of the G11/G12 and G13/Go combinations), there were no significant differences in the content of any of the G proteins analyzed.