TY - JOUR
T1 - Alteration of brain cell membrane function following cocaine exposure in the fetal guinea pig
AU - Lien, Reyin
AU - Mishra, Om P.
AU - Graham, Ernest
AU - Delivoria-Papadopoulos, Maria
AU - Anday, Endla K.
N1 - Funding Information:
Acknowledgements. The authors wish to thank Johanna Kubm for the techmcal assistance she provided m the course of this study Supported by NIH grants HD-20337 and HL-37421.
PY - 1994/2/21
Y1 - 1994/2/21
N2 - 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 μmol Pi/mg protein/h, cocaine vs. control, respectively, (P < 0.01) and was similar to the hypoxia group (21.9 ± 2.8 μmol Pi/mg protein/h). The products of lipid peroxidation did not change significantly following cocaine hypoxia resulted in a rise in CD from 0 to 0.175 ± 0.015 μmol/g brain, control vs. hypoxia, (P < 0.01), and FC from 1.13 ± 0.15 to 1.88 ± 0.13 μg quinine sulf 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.
AB - 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 μmol Pi/mg protein/h, cocaine vs. control, respectively, (P < 0.01) and was similar to the hypoxia group (21.9 ± 2.8 μmol Pi/mg protein/h). The products of lipid peroxidation did not change significantly following cocaine hypoxia resulted in a rise in CD from 0 to 0.175 ± 0.015 μmol/g brain, control vs. hypoxia, (P < 0.01), and FC from 1.13 ± 0.15 to 1.88 ± 0.13 μg quinine sulf 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.
KW - Brain cell membrane injury
KW - Cocaine
KW - Na,K-ATPase
KW - Newborn
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U2 - 10.1016/0006-8993(94)91240-8
DO - 10.1016/0006-8993(94)91240-8
M3 - Article
C2 - 8180803
AN - SCOPUS:0028153537
SN - 0006-8993
VL - 637
SP - 249
EP - 254
JO - Brain research
JF - Brain research
IS - 1-2
ER -