Ethanol and phosphatidylethanol reduce the binding of [3H]inositol 1,4,5-trisphosphate to rat cerebellar membranes.
In this study, we have analysed the effect of ethanol and phosphatidylethanol, a unique phospholipid formed only in the presence of ethanol, on the binding of [3H]inositol 1,4,5-trisphosphate to rat cerebellar membranes. Rats were intraperitoneally injected daily with 3 g of ethanol/kg body weight for different periods of time. Repeated administration of ethanol induced a reduction in the binding capacity (Bmax) without affecting the affinity constant (Kd). A significant 32% reduction was observed after 21 days of exposure (from control Bmax values of 25 +/- 3 pmol/mg and Kd values of 9 +/- 2 nM). In an in-vitro assay, phosphatidylethanol (500 microM) and phosphatidic acid (500 microM, but no other phospholipids tested, induced a reduction in Bmax (39% and 43%, respectively). The observed effect displayed by phosphatidylethanol was not due to its degradation to phosphatidic acid or other phospholipids. The results emphasize the importance of examining phosphatidylethanol (PEth) as a possible mediator of the effects of ethanol on cellular processes. However, the role of PEth in the observed effect of long-term ethanol exposure still needs further consideration.
Rodríguez
F D
FD
Department of Biochemistry and Molecular Biology, University of Salamanca, Spain.
Lundqvist
C
C
Alling
C
C
Gustavsson
L
L
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects*; D000431:Ethanol / Q000633:toxicity*; D020404:Glycerophospholipids; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008297:Male; D010712:Phosphatidic Acids / Q000633:toxicity*; D011869:Radioligand Assay; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects; D013570:Synaptic Membranes / Q000187:drug effects*
D015220:Calcium Channels; D020404:Glycerophospholipids; D053496:Inositol 1,4,5-Trisphosphate Receptors; D010712:Phosphatidic Acids; D018160:Receptors, Cytoplasmic and Nuclear; C051521:phosphatidylethanol; D000431:Ethanol; D015544:Inositol 1,4,5-Trisphosphate