Interaction of ethanol and anoxia with muscarinic receptor--stimulated phosphoinositide metabolism during brain development.
The mechanism(s) by which ethanol induces alterations in brain development may involve direct actions (e.g. changes in specific biochemical pathways), or indirect effects, such as cerebral hypoxia resulting from ethanol - induced circulatory changes. Since both ethanol and hypoxia are known to affect the metabolism of phosphoinositides, which has been suggested as a possible target for ethanol's developmental neurotoxicity, in the present study we have investigated the in vitro effects of both severe hypoxia (anoxia) and ethanol (alone or in combination) on muscarinic receptor-stimulated phosphoinositide metabolism in cerebral cortex slices from neonatal rats. Anoxia markedly inhibited carbachol - stimulated phosphoinositide metabolism in adult rats (67%), but only slightly (10%) in neonatal animals. Reoxygenation reversed the effect of anoxia at both ages. On the other hand, ethanol's inhibitory effect was pronounced in neonatal rats only, and was additive to that of anoxia. The presence of ethanol did not affect the recovery of carbachol - stimulated phosphoinositide metabolism following anoxia and reoxygenation. These results indicate that ethanol and anoxia differently and independently affect muscarinic receptor - stimulated phosphoinositide metabolism and may mutually contribute to the CNS effects observed following developmental ethanol exposure.
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D002534:Hypoxia, Brain / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D000431:Ethanol