Alpha7 nicotinic receptor mediated protection against ethanol-induced cytotoxicity in PC12 cells.
Ethanol caused a concentration-dependent loss of PC12 cells over a 24 h interval, accompanied by an increase in intracellular calcium. The specific alpha7 nicotinic receptor partial agonist DMXB attenuated both of these ethanol-induced actions at a concentration (3 microM) found previously to protect against apoptotic and necrotic cell loss. The alpha7 nicotinic receptor antagonist methylylaconitine blocked the neuroprotective action of DMXB when applied with but not 30 min after the agonist. These results indicate that activation of alpha7 nicotinic receptors may be therapeutically useful in preventing ethanol-neurotoxicity.
Li
Y
Y
Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL 32610, USA.
King
M A
MA
Grimes
J
J
Smith
N
N
de Fiebre
C M
CM
Meyer
E M
EM
D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D001597:Benzylidene Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D016716:PC12 Cells / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011978:Receptors, Nicotinic / Q000502:physiology*; D014966:Xanthenes / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000814:Aniline Compounds; D001597:Benzylidene Compounds; C579165:Chrna7 protein, rat; D005456:Fluorescent Dyes; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D014966:Xanthenes; D064569:alpha7 Nicotinic Acetylcholine Receptor; C059715:Fluo-3; D000431:Ethanol; C088936:3-(2,4-dimethoxybenzylidene)anabaseine; D002118:Calcium