Alcohol and membrane-associated signal transduction

¹Department of Pathology and Cell Biology, Jefferson Medical College, Philadelphia, PA 19107.

Alcohol and Alcoholism (Oxford, Oxfordshire)

|January 1, 1990

Summary

Ethanol affects cell signaling by activating phospholipase C and altering calcium and diacylglycerol levels. Chronic intake may lead to tolerance, potentially involving protein kinase C.

Area of Science:

Biochemistry
Cellular Biology
Pharmacology

Background:

Ethanol interacts with membrane-associated signal transduction pathways.
These pathways involve phospholipases and their phospholipid substrates.

Purpose of the Study:

To investigate ethanol's effects on signal transduction mechanisms.
To explore the role of phospholipases in ethanol's action.
To understand tolerance development to ethanol's effects.

Main Methods:

Studied ethanol's activation of polyphosphoinositide-specific phospholipase C in cell and membrane preparations.
Examined ethanol's influence on intracellular signaling, including Ca2+ release and diacylglycerol formation.
Investigated ethanol's interaction with phospholipase D and phosphatidylethanol formation.
Analyzed ethanol-induced feedback inhibition and desensitization in liver cells.
Explored the role of protein kinase C in tolerance to ethanol.

Main Results:

Ethanol activates phospholipase C, leading to inositol-1,4,5-trisphosphate formation, Ca2+ release, and protein kinase C stimulation.
Ethanol's activation of phospholipase C is linked to its interaction with the receptor-G-protein-phospholipase C complex.
Ethanol induces feedback inhibition of phospholipase C in liver cells, causing desensitization to agonists.
Ethanol interacts with phospholipase D, potentially forming phosphatidylethanol.
Tolerance to ethanol's effects on signal transduction can develop after chronic intake, with protein kinase C implicated.

Conclusions:

Ethanol significantly impacts cellular signaling by modulating phospholipase activity and second messenger formation.
Ethanol can disrupt physiological control mechanisms through its effects on signal transduction pathways.
Protein kinase C may play a crucial role in the cellular tolerance to ethanol observed after chronic exposure.

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Alcohol and membrane-associated signal transduction

Area of Science:

Background:

Purpose of the Study:

Main Methods:

Main Results:

Conclusions:

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