Interaction of ethanol with muscarinic receptor-stimulated phosphoinositide metabolism during the brain growth spurt in the rat: role of acetaldehyde.
The developing brain is extremely sensitive to the neurotoxicity of ethanol; however, the mechanism(s) of its developmental neurotoxicity are still elusive. In the developing rat brain, ethanol exerts an age-, brain region-, and receptor-specific inhibitory effect on muscarinic receptor-stimulated phosphoinositide metabolism, which may be linked to some of the neurotoxic effects of ethanol found in children with fetal alcohol syndrome. Since some studies have suggested that the ethanol metabolite acetaldehyde may mediate, at least in part, the developmental effects of ethanol, in the present study we have examined whether acetaldehyde would inhibit carbachol-stimulated phosphoinositide metabolism in brain slices from immature rats. We also tested propionaldehyde, the corresponding aldehyde of n-propanol, another alcohol shown to cause microencephaly and to affect phosphoinositide metabolism in the developing rat. Neither acetaldehyde nor propionaldehyde, at concentrations up to 1 mM, had any inhibitory effect on this system, while the two alcohols did, as previously reported. These results suggest that ethanol itself may be the primary agent responsible for its developmental neurotoxicity.
Tan
X X
XX
Department of Environmental Health, University of Washington, Seattle 98195.
Castoldi
A F
AF
Manzo
L
L
Costa
L G
LG
D000433:1-Propanol / Q000633:toxicity; D000079:Acetaldehyde / Q000633:toxicity*; D000375:Aging / Q000502:physiology*; D000447:Aldehydes / Q000633:toxicity; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009928:Organ Specificity; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*
D000447:Aldehydes; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D000431:Ethanol; D002217:Carbachol; D000433:1-Propanol; C005556:propionaldehyde; D000079:Acetaldehyde