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Effects of Ethanol on Inositol 1,3,4,5‐Tetrakisphosphate Metabolism by Rat Brain Homogenates
Author(s) -
Chandler L. Judson,
Kurian Pawels,
Crews Fulton T.
Publication year - 1991
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1991.tb00531.x
Subject(s) - dephosphorylation , inositol , second messenger system , inositol phosphate , biochemistry , phosphatase , ethanol , chemistry , metabolism , phosphorylation , signal transduction , sugar phosphates , intracellular , biology , enzyme , receptor
The hydrolysis of membrane phosphoinositides is widely recognized as an important signal transduction pathway in brain. One of the products of phosphoinositide hydrolysis, Ins (1,4,5)P 3 , is thought to participate in signal transduction by mobilizing intracellular calcium and it is now clear that Ins(1,4,5)P 3 metabolism is a complicated process that may be highly regulated. In addition to being dephos‐phorylated by the action of a 5‐phosphatase, Ins(1,4,5)P 3 can be phosphorylated by a 3‐kinase to Ins(1,3,4,5)P 4 . Although the physiological significance of the higher inositol polyphosphates is not clear, recent evidence suggests that Ins(1,3,4,5)P 4 may also have important second messenger function. Since ethanol is known to have potent effects on synaptic transmission, we investigated the in vitro effects of ethanol on [ 3 H]Ins(1,3,4,5)P 4 metabolism by rat whole brain homogenates. Ins(1,3,4,5)P 4 was rapidly hydrolyzed to Ins(1,3,4)P 3 , inositol bisphosphates [Ins(3,4)P 2 and Ins(1,3)P 2 ], inositol monophosphates [Ins(l)P/Ins(B)P and Ins(4)P], and to inositol by sequential dephosphorylation. No [ 3 H]Ins(1,4,5)P 3 was detected. Ethanol (500 mM), significantly accelerated the dephosphorylation of Ins(1,4,5)P 3 , resulting in a more rapid formation of inositol bisphosphates, monophosphates and inositol. However, intoxicating and sedative‐hypnotic concentrations of ethanol (30‐100 mM) had no effect upon Ins(1,3,4)P 3 dephosphorylation, suggesting that pharmacologically relevant concentrations of ethanol do not directly effect the enzymes involved in the dephosphorylation of Ins(1,3,4,5)P 4 to free inositol in brain.