Developmental neurotoxicity of ethanol: in vitro inhibition of muscarinic receptor-stimulated phosphoinositide metabolism in brain from neonatal but not adult rats.
The in vitro effects of ethanol (EtOH) on muscarinic receptor-stimulated phosphoinositide metabolism were measured in cerebral cortex slices of adult and 7-day-old rats. EtOH (500 mM) caused a significant decrease (32-43%) of maximal accumulation of [3H]inositol phosphates (InsPs) induced by carbachol, and a 2-fold increase in its EC50 in 7-day-old rats, but had no effect in adult rats. The effect of EtOH on [3H]InsPs accumulation in neonatal rats was significant at a concentration as low as 150 mM. The inhibitory effect of EtOH was maximal in cerebral cortex and hippocampus and lower in cerebellum, while no effect was observed in the brainstem. While carbachol- and acetylcholine-stimulated phosphoinositide metabolism were inhibited by EtOH, EtOH had no effect on norepinephrine-, histamine-, and serotonin-stimulated phosphoinositide hydrolysis. These results are qualitatively and quantitively similar to those previously found following in vivo administration of EtOH to developing and to adult rats, suggesting that the muscarinic receptor-stimulated phosphoinositide metabolism might represent a target for EtOH-induced developmental neurotoxicity.
Balduini
W
W
Department of Environmental Health, University of Washington, Seattle 98195.
Costa
L G
LG
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D000431:Ethanol / Q000633:toxicity*; D066298:In Vitro Techniques; D010716:Phosphatidylinositols / Q000493:pharmacokinetics*; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism
D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D000431:Ethanol; D002217:Carbachol