Phosphotidylethanol mimics ethanol modulation of p42/44 mitogen-activated protein kinase signalling in hepatocytes.
OBJECTIVE
Although long-term exposure of hepatocytes to ethanol results in agonist-selective potentiation of p42/44 mitogen-activated protein kinase (MAPK) activation, mediators of this effect of ethanol are not known.


METHODS
We examined the role of phosphatidylethanol (PEth), a novel phospholipid formed exclusively in the presence of ethanol.


RESULTS
PEth accumulated in primary cultures of rat hepatocytes treated with ethanol. Exogenously added PEth potentiated angiotensin II-stimulated p42/44 MAPK similarly to that observed with ethanol treatment of cells for 24 h, a condition where PEth accumulates. PEth levels remained elevated 2 h after ethanol removal subsequent to a 24-h exposure, and the potentiating effects of ethanol were also present. PEth did not potentiate p42/44 MAPK activation by either epidermal growth factor or vasopressin, thus further mimicking the known agonist selectivity for this ethanol effect.


CONCLUSIONS
These results offer a novel role for PEth as a mediator in the ethanol modulation of p42/44 MAPK cascade in hepatocytes.
Aroor
Annayya R
AR
Department of Pharmacology, School of Medicine, University of Missouri-Columbia, School of Medicine, Columbia, MO 65212, USA.
Custer
Geoffrey W
GW
Weng
Yu-I
YI
Lee
Youn Ju
YJ
Shukla
Shivendra D
SD
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D020404:Glycerophospholipids / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002492:Central Nervous System Depressants; D020404:Glycerophospholipids; D014662:Vasoconstrictor Agents; C051521:phosphatidylethanol; D000804:Angiotensin II; D000431:Ethanol; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases