The ability of divalent cations to enhance ethanol-induced sleeping time.
This investigation was carried out to determine if prolongation of ethanol-induced sleep by divalent cations is mediated by calmodulin (CaM) and biogenic amine. The effects of CaM antagonist, W-7:[N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide], serotonin (5-HT) synthesizing enzyme inhibitor, p-chlorophenylalanine (PCPA), and catecholamine synthesizing enzyme inhibitor, alpha-methyltyrosine (alpha MPT) on ethanol-induced sleeping time enhanced by divalent cations were studied in ddY male mice. The ethanol-induced sleeping time was increased by 70, 200, 180, 70, and 45% by intraventricular (IVT) injection of CaCl2 (10 mumol/kg), MnCl2 (15 mumol/kg), ZnCl2 (2.5 mumol/kg), CdCl2 (1 mumol/kg), and HgCl2 (1 mumol/kg), respectively, compared to the saline group. On the other hand, when mice were treated IVT with W-7 and their divalent cation, the sleeping time induced by ethanol was decreased compared to that of the cation without W-7 treated mice. Also, when mice were injected simultaneously with either PCPA or alpha MPT and CaCl2, ZnCl2, CdCl2, or HgCl2, the ethanol-induced sleeping time was less compared to those given saline together with their cation, respectively. These results would suggest a probable mechanism in which Ca++, Zn++, Cd++, and Hg++ prolong ethanol-induced sleeping time by activating biogenic amine synthesizing enzymes through cerebral CaM and CaM-dependent protein kinase.
D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002413:Cations, Divalent / Q000494:pharmacology*; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D010134:Fenclonine / Q000494:pharmacology; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D051379:Mice; D012890:Sleep / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology; D019805:alpha-Methyltyrosine
D002147:Calmodulin; D002413:Cations, Divalent; D008781:Methyltyrosines; D013449:Sulfonamides; D014665:Vasodilator Agents; D000431:Ethanol; C017967:W 7; D019805:alpha-Methyltyrosine; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; D010134:Fenclonine