PMID: 9174651May 1, 1997Paper

Inhibition of hepatic inositol 1,4,5-trisphosphate receptor function by ethanol and other short chain alcohols

Cell Calcium
D C Renard-RooneyA P Thomas

Abstract

The ability of alcohols to regulate InsP3-receptor activity was examined in permeabilized hepatocytes. Incubation with 30-300 mM ethanol decreased the sensitivity to InsP3 for Ca2+ release, with little effect on the size of the Ca2+ store that could be released with maximal concentrations of InsP3. Ethanol (300 mM) increased the EC50 for InsP3 from a control value of 134.0 +/- 13.5 nM to 220.0 +/- 25.9 nM. Although ethanol also caused a partial depletion of the total pool of stored Ca2+, the ethanol-induced shift in InsP3 sensitivity was not secondary to this alteration in Ca2+ loading. Partial depletion of the Ca2+ stores with low doses of ionomycin and thapsigargin did not cause a shift in InsP3 sensitivity. Furthermore, measurements of InsP3 receptor channel activity using retrograde flux of Mn2+ to quench the fluorescence of Fura-2 within the Ca2+ stores demonstrated that ethanol inhibited InsP3-activated channel activity in the absence of stored Ca2+. Other short chain alcohols (methanol, 1-propanol and 1-butanol) also decreased the efficacy of InsP3 to release Ca2+. Measurements of [3H]-InsP3 binding demonstrated that ethanol decreased the total number of InsP3 binding sites without changing the KD. The effect of ethanol ...Continue Reading

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Citations

Jan 12, 2000·Alcoholism, Clinical and Experimental Research·S BokkalaS K Joseph
Jun 8, 2001·Alcoholism, Clinical and Experimental Research·S D ShuklaJ B Hoek
Oct 31, 2009·Journal of Pediatric Hematology/oncology·Louise Olde NordkampHenk van den Berg
Oct 16, 2014·American Journal of Physiology. Endocrinology and Metabolism·Colleen N FeriodBarbara E Ehrlich
Feb 20, 2021·Function·Lawrence D GaspersPaula J Bartlett

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