Chronic ethanol treatment reduces adenylyl cyclase activity in human erythroleukemia cells.
Characteristic changes of platelet membrane adenylyl cyclase activity have been described in men with alcoholism. We studied the occurrence of these changes in human erythroleukemia (HEL) cells after chronic ethanol treatment. Chronic treatment of the HEL cell with ethanol (50 or 100 mM) for 48 h resulted in significant reduction of prostaglandin E1-stimulated adenylyl cyclase activity. The acute ethanol (200 mM, 5 min) enhancement of adenylyl cyclase activity was significantly reduced after chronic ethanol treatment. We also observed a reduction in phorbol-12,13-dibutyrate (PDB) enhancement of prostaglandin E1-stimulation after chronic ethanol treatment. Chronic ethanol treatment (50 or 100 mM) reduced the activity of adenylyl cyclase in response to stimulation by acute ethanol to a greater extent than that of after acute PDB. The increase in cAMP formation by ethanol and PDB was only evident when prostaglandin E1 was present and under basal conditions (when no stimulatory agent was present) ethanol up to 200 mM, and PDB up to 1 M, had no significant effect on adenylyl cyclase activity. The reduced capacity of ethanol and/or PDB to stimulate adenylyl cyclase activity after chronic ethanol treatment suggests the involvement of a common denominator in the action of ethanol and PDB.
Rabbani
M
M
Department of Pharmacology, Isfahan University of Medical Sciences, School of Pharmacy, Hezar Jerib Avenue, Isfahan, Iran. rabanim@yahoo.com
Tabakoff
B
B
D000262:Adenylyl Cyclases / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D000242:Cyclic AMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects
D011458:Prostaglandins E; D015240:Phorbol 12,13-Dibutyrate; D000431:Ethanol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases