Ethanol and inositol 1,4,5-trisphosphate mobilize calcium from rat brain microsomes.
The effects of ethanol on ATP-dependent Ca2+ uptake and inositol 1,4,5-trisphosphate (Ins-P3)-induced Ca2+ release were assessed in rat cerebellar and cortical microsomes. Ins-P3, 0.2-10 microM, released 7-14% of ATP loaded microsomal Ca2+ stores after a 15-sec exposure. Ethanol, 250-750 mM, added after ATP-dependent loading, significantly released microsomal Ca2+ stores, and the amount released was additive to that seen with Ins-P3 alone. The presence of ethanol, 250-750 mM, during the ATP-dependent loading period, resulted in decreased Ca2+ uptake that correlated with decreases in Ins-P3-induced Ca2+ release. Chronic ethanol treatment failed to produce any alterations in ethanol's ability to promote Ca2+ release or to inhibit ATP-dependent Ca2+ uptake. Furthermore, Ins.-P3-induced Ca2+ release was not altered by chronic ethanol treatment. These results suggest that Ins-P3 sensitive Ca2+ stores are resistant to pharmacologically relevant concentrations of ethanol, and do not appear to be involved in the chronic cellular effects of ethanol.
Machu
T
T
University of Texas, College of Pharmacy, Austin 78712.
Woodward
J J
JJ
Leslie
S W
SW
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000428:Alcohol Drinking / Q000502:physiology; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism*; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D008861:Microsomes / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000431:Ethanol; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D002118:Calcium