Effects of prenatal ethanol exposure on N-methyl-D-aspartate-mediated calcium entry into dissociated neurons.
The effects of prenatal ethanol exposure on N-methyl-D-aspartate (NMDA)-activated calcium entry into dissociated neurons were studied. Dissociated brain cells were isolated from less than 1-day-old pups from prenatally ethanol-exposed, pair-fed control and ad libitum control groups and loaded with fura-2. Prenatal ethanol exposure significantly decreased the NMDA receptor-mediated calcium entry compared to both pair-fed and ad libitum control groups. To determine the mechanisms of the prenatal ethanol exposure on the NMDA-mediated ion channel decrements, possible modulatory sites of the NMDA receptor were studied. Glycine (0.1, 1, 10 and 100 microM) increased calcium entry to an equal extent in the ethanol and control groups, but did not reverse the effect of prenatal ethanol exposure. Furthermore, low concentrations of MK801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5-10-imine hydrogen maleate] (25 and 50 nM) did not further inhibit calcium entry beyond that observed with the prenatal ethanol exposure, but significantly inhibited control group responses. Mg++ showed a similar result. With increasing concentrations of Mg++ the calcium entry in the three groups tended to converge. Thus, these results suggest that prenatal ethanol exposure inhibits the function of NMDA receptor-mediated ion channels by possibly altering the structural properties of the ion channel itself and/or by interacting with inner ion channel modulatory sites activated by Mg++ or MK801, and not the glycine site.
Lee
Y H
YH
Division of Pharmacology and Toxicology, University of Texas at Austin.
Spuhler-Phillips
K
K
Randall
P K
PK
Leslie
S W
SW
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D005998:Glycine / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D008274:Magnesium; D002118:Calcium; D005998:Glycine