Abstract
The present study examines the hypothesis that morphine exposure alters newborn brain vascular endothelial cell production of endothelin (ET)-1, as well as the mRNA expression of its receptors. Newborn piglet vascular endothelial cells were treated with morphine (100 ng/mL media), naloxone (100 ng/mL media), or drug-free media (control) for 6, 24, 48, and 96 h. Media was analyzed for ET-1 and big ET-1 levels and the cells were assessed for ETA and ETB receptor mRNA expression. Morphine exposure progressively increased ET-1 production from 6 to 96 h with concurrent reductions in big ET-1 levels starting at 24 h to almost undetectable levels by 96 h. Whereas ETA receptor mRNA expression increased 2-fold at 6 h and 4-fold at 96 h, ETB receptor mRNA expression remained unchanged. Naloxone exposure caused significant decreases in ET-1 levels, whereas an opposite effect was noted in big ET-1 levels, which increased from 6 through 96 h. Naloxone caused a progressive decrease in ETA receptor mRNA expression at 6 h through 96 h and a 2-fold increase in ETB receptor mRNA expression at 48 and 96 h. Increased ET-1 and its receptors in response to morphine may suggest altered cerebrovascular perfusion and brain metabolism in the immature piglet brain.
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Abbreviations
- ECE:
-
endothelin converting enzyme
- ET-1:
-
endothelin-1
- EtBr:
-
ethidium bromide
- IVH:
-
intraventricular hemorrhage
- NO:
-
nitric oxide
- PVL:
-
periventricular leukomalacia
- TFA:
-
trifluoroacetic acid
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Supported by grants from the Long Beach Memorial Medical Center Foundation, Long Beach, California, and the Medical Research Council of Canada, Ottawa, Canada.Presented, in part, at the 1999 Society for Pediatric Research Meeting in Boston, Massachusetts.
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Van Woerkom, R., Beharry, K., Modanlou, H. et al. Influence of Morphine and Naloxone on Endothelin and its Receptors in Newborn Piglet Brain Vascular Endothelial Cells: Clinical Implications in Neonatal Care. Pediatr Res 55, 147–151 (2004). https://doi.org/10.1203/01.PDR.0000100756.32861.60
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DOI: https://doi.org/10.1203/01.PDR.0000100756.32861.60
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