Cut-off phenomenon in the protective effect of alcohols against lysophosphatidylcholine-induced calcium overload.
We studied the effect of chain length on the protective effect of alcohols against lysophosphatidylcholine (LPC)-induced Ca2+ overload in neonatal rat cardiomyocytes. We previously found that ethanol retards Ca2+ elevation. Cells were loaded with the Ca2+-sensitive fluorophore fura-2, and changes in fluorescence were followed. The addition of 10 microM LPC increased Ca2+, which reached a plateau after an 8-10 min delay. The presence of 88 mM n-propanol, n-butanol, tert-butanol, or 2,2-dimethylpropanol significantly increased the delay by 94-213%. However, n-pentanol at 2 mM or 88 mM had no protective effect. Among n-alcohols, the increase in lag time was inversely proportional to the length of the carbon chain. Chain length, rather than molecular weight determines the effect, because 2,2-dimethylpropanol had a protective effect. The influence of alcohols on LPC micelle formation was estimated from the increase in octadecyl rhodamine B fluorescence; the increase by n-alcohols was directly proportional to chain length, indicating that micelle formation was not involved in the extension of lag time. The absence of the protective effect when the alcohol aliphatic chain exceeds four carbons suggests that the effect of ethanol may be mediated via a small lipophilic pocket on a protein, or to lateral pressure perturbation in the membrane.
Bordeleau
Louis-Jean
LJ
Quebec Heart Institute, Laval Hospital Research Center, 2725 chemin Ste-Foy, Ste-Foy, QC, Canada, G1V 4G5.
Gailis
Laimonis
L
Fournier
Dominique
D
Morissette
Marc
M
Di Paolo
Thérèse
T
Daleau
Pascal
P
D020001:1-Butanol / Q000494:pharmacology; D000433:1-Propanol / Q000494:pharmacology; D000438:Alcohols / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D006321:Heart / Q000187:drug effects; D008244:Lysophosphatidylcholines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008823:Micelles; D032383:Myocytes, Cardiac / Q000187:drug effects*; D000439:Pentanols / Q000494:pharmacology; D020005:Propanols / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D020002:tert-Butyl Alcohol / Q000494:pharmacology
D000438:Alcohols; D005456:Fluorescent Dyes; D008244:Lysophosphatidylcholines; D008823:Micelles; D000439:Pentanols; D020005:Propanols; D000431:Ethanol; C505606:2,2-dimethylpropanol; D020001:1-Butanol; D000433:1-Propanol; C024999:n-pentanol; D020002:tert-Butyl Alcohol; D002118:Calcium; D016257:Fura-2