Effects of ethanol in vivo and in vitro on stimulated phosphoinositide hydrolysis in rat cortex and cerebellum.
The effects of ethanol on phosphoinositide (PI) hydrolysis in rat cortex and cerebellum were studied to determine if this signal transduction mechanism is a pharmacological site of action for ethanol. In addition PI responses in young adult (8 months old) and old (22 months old) rats were compared to investigate the possible interaction between chronic ethanol treatment and aging on stimulated inositide metabolism. Fischer 344 rats were maintained on a nutritionally complete liquid diet containing sucrose or ethanol for 5 months. PI hydrolysis in prelabeled cortical or cerebellar slices was determined by measuring the release of [3H]inositol phosphates in the presence of 8 mM LiCl. Neither chronic ethanol nor aging altered maximal PI responses to carbachol or submaximal responses elicited by 20 mM KCl or 30 microM A23187. The glutamate-induced response was slightly reduced in the aged rats. Concentration-effect curves for norepinephrine (NE)-stimulated PI hydrolysis were similar in sucrose- and ethanol-treated cortex and cerebellum. Ethanol in vitro inhibited NE-stimulated PI hydrolysis in cortical but not cerebellar slices. The ethanol-induced inhibition of the NE-stimulated PI response was not altered by aging or chronic ethanol treatment. These results suggest that aging or chronic ethanol treatment do not cause large changes in the responsiveness of most PI-linked receptors, and thus, any deficits caused by these conditions may not be due to functional changes in receptor-mediated PI hydrolysis.
Gonzales
R A
RA
Department of Pharmacology, University of Florida Medical School, Gainesville.
Crews
F T
FT
D000367:Age Factors; D000428:Alcohol Drinking / Q000502:physiology; D000818:Animals; D002531:Cerebellum / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects*; D046508:Culture Techniques; D000431:Ethanol / Q000494:pharmacology*; D006868:Hydrolysis; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D011956:Receptors, Cell Surface / Q000187:drug effects*; D018160:Receptors, Cytoplasmic and Nuclear
D010716:Phosphatidylinositols; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; C040985:phosphatidylinositol receptors; D000431:Ethanol; D009638:Norepinephrine