The inhibition of [3H] inositol 1,4,5-trisphosphate binding by Ca2+is modified after long-term ethanol treatment and ethanol withdrawal

Abstract

We have analysed the influence of long-term ethanol exposure on the effect exerted by Ca²⁺ on the binding of tritiated inositol 1,4,5-trisphosphate to its receptors in rat cerebellar membranes. After 21 days of ethanol treatment the binding of the agonist was reduced in the absence of Ca²⁺. The decrease was due to reduction in B max without any alteration of K d. In membranes from control animals Ca²⁺ inhibited the binding of InsP₃ in a dose-dependent manner by altering the affinity of the protein for the ligand. However, the inhibitory effect of Ca²⁺ was abolished following chronic ethanol exposure. Five days after withdrawing ethanol, the B max recovered to control values, but the inhibitory effect of Ca²⁺ was recovered at only 10 days after withdrawal. The results indicate that long-term ethanol exposure may have differential effects on the InsP₃binding site and on the Ca²⁺ binding site, or alternatively on a Ca²⁺ -related regulatory cycle.