Alteration of brain cell membrane function following cocaine exposure in the fetal guinea pig.
The effect of cocaine on brain cell membrane structure and function was studied in the fetal guinea pig. We tested the hypothesis that cocaine, a potent vasoconstrictor, would result in brain cell membrane dysfunction as determined by altered activity of Na+,K(+)-ATPase and the appearance of products of membrane lipid peroxidation (conjugated dienes (CD) and fluorescent compounds (FC)). A total of 14 pregnant guinea pigs were studied at term (60 days). One hour prior to delivery, the pregnant guinea pigs were divided into 3 groups as follows: cocaine, 30 mg/kg i.p., saline placebo i.p., or 7% FiO2 for 1 h. Following cocaine, brain Na+,K(+)-ATPase activity decreased (mean +/- S.D., 25.6 +/- 9.2 vs. 54.6 +/- 3.4 mumol Pi/mg protein/h, cocaine vs. control, respectively, P < 0.01) and was similar to the hypoxia group (21.9 +/- 2.8 mumol Pi/mg protein/h). The products of lipid peroxidation did not change significantly following cocaine whereas hypoxia resulted in a rise in CD from 0 to 0.175 +/- 0.015 mumol/g brain, control vs. hypoxia, (P < 0.01), and FC from 1.13 +/- 0.15 to 1.88 +/- 0.13 micrograms quinine sulfate/g brain, control vs. hypoxia, (P < 0.01). These data show that acute fetal cocaine exposure, unlike hypoxia alone, results in a significant decrease in Na+,(K+)-ATPase activity without a significant increase in the products of lipid peroxidation, suggesting the mechanism by which cocaine affects brain cell membrane integrity is distinct from hypoxia. Inhibition of the enzyme activity may be due to a direct action of cocaine on the enzyme or due to enzyme regulation by cocaine-induced alterations in neurotransmitters.
Lien
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Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia 19104.
Mishra
O P
OP
Graham
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Delivoria-Papadopoulos
M
M
Anday
E K
EK
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000648:ultrastructure; D002462:Cell Membrane / Q000187:drug effects; D003042:Cocaine / Q000633:toxicity*; D005260:Female; D005456:Fluorescent Dyes; D006168:Guinea Pigs; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D011247:Pregnancy; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism
D005456:Fluorescent Dyes; D000254:Sodium-Potassium-Exchanging ATPase; D003042:Cocaine