Ethanol-induced hydrolysis of brain sialoglycoconjugates in the rat: effect of sialic acid in antagonizing ethanol intoxication.
Several reports indicate that acute ethanol promotes the cleavage of brain sialoglycoconjugates (SGC). We attempted to confirm this effect by monitoring cleavage of sialic acid (SA) that had been radiolabeled by pretreatment with the specific precursor of SA, N-[3H]acetyl-D-mannosamine, injected intracerebroventricularly into rats 20 h prior to ethanol injection (2 or 3 g/kg, given four times in a simulated "binge drinking" protocol). Analysis of the residual labeled material revealed a significant reduction of radiolabel (p less than 0.01), as compared to saline controls. A dose of 3 g/kg diminished the total labeled SGC by half. Brain sialidase activity was not affected by the ethanol treatment. Since ethanol intoxication is associated with enhanced SA cleavage, one hypothesis needing testing is that loss of SA might help to cause intoxication. If so, pretreatment with SA might antagonize intoxication, presumably by offsetting loss due to cleavage of SA. Consistent with our earlier results, we found that when sialic acid was given i.p. (25 mg/kg), 1, 6, or 24 h prior to ethanol injection (4 g/kg, i.p.), the sleep time was reduced by 35-40% and the performance on rotorod was significantly enhanced (p less than 0.01). When ethanol was replaced by pentobarbital (40 mg/kg), the sleep time was increased (approximately 30%) at 6 h after injection with either 25 or 100 mg/kg sialic acid, whereas at the 24 h postinjection it was decreased (approximately 20%) at both doses. The results suggest that sialic acid is a key component in mediating ethanol effects and perhaps also, in a different way, anesthetic effects.
Cherian
L
L
Department of Veterinary Anatomy, Texas A&M University, College Station 77843-4458.
Mathew
J
J
Klemm
W R
WR
D000435:Alcoholic Intoxication / Q000201:enzymology / Q000517:prevention & control*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D005732:Gangliosides / Q000378:metabolism*; D006017:Glycolipids / Q000378:metabolism*; D006595:Hexosamines / Q000378:metabolism; D008297:Male; D009048:Motor Skills / Q000187:drug effects; D019158:N-Acetylneuraminic Acid; D009439:Neuraminidase / Q000378:metabolism; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D012794:Sialic Acids / Q000008:administration & dosage* / Q000378:metabolism; D012894:Sleep Stages / Q000187:drug effects
D005732:Gangliosides; D006017:Glycolipids; D006595:Hexosamines; D012794:Sialic Acids; C009255:sialoglycolipids; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid; D010424:Pentobarbital; C002022:N-acetylmannosamine