Inhibition of the cerebellar inositol 1,4,5-trisphosphate-sensitive Ca2+ channel by ethanol and other aliphatic alcohols.
The effects of ethanol and other aliphatic alcohols on the endoplasmic reticulum Ca2+ pump and the inositol 1,4,5-trisphosphate (InsP3)-sensitive Ca2+ channel were studied in pig cerebellar microsomes. Methanol, ethanol and propanol all stimulated ATP-dependent Ca2+ uptake, whereas butanol inhibited this process. Ethanol inhibited InsP3-induced Ca2+ release [half-maximal inhibition at 3.5%, v/v (600 mM)]. However, ethanol affected only the amount of InsP3-releasable Ca2+, without affecting the concentration of InsP3 required to induce half-maximal release. Other alcohols of longer chain length were more potent than ethanol at inhibiting InsP3-induced Ca2+ release, but none of the alcohols tested affected [3H]InsP3 binding to its receptor. Using stopped-flow techniques, measurements of the rate of InsP3-induced Ca2+ release in the preparation of pig cerebellar microsomes used in this study showed the kinetics to be monophasic, with a rate constant of 0.93s-1 at 20 microM InsP3. This rate constant was dependent upon InsP3 concentration, decreasing to 0.38s-1 at 0.25 microM InsP3. Ethanol was shown to reduce the fractional amount of InsP3-induced Ca2+ release without significantly affecting the rate constant for this process.
Mezna
M
M
School of Biochemistry, University of Birmingham, Edgbaston, U.K.
Patchick
T
T
Tovey
S
S
Michelangeli
F
F
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000438:Alcohols / Q000494:pharmacology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D007700:Kinetics; D008861:Microsomes / Q000378:metabolism; D013053:Spectrophotometry; D013552:Swine
D000438:Alcohols; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D000001:Calcimycin; D000431:Ethanol; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases; D002118:Calcium