Influence of morphine and naloxone on endothelin and its receptors in newborn piglet brain vascular endothelial cells: clinical implications in neonatal care.
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.
Van Woerkom
Richard
R
Division of Neonatology-Perinatal Medicine, Department of Pediatrics, University of California, Irvine, California 92868, USA.
Beharry
Kay D A
KD
Modanlou
Houchang D
HD
Parker
Jacqueline
J
Rajan
Vigna
V
Akmal
Yasir
Y
Aranda
Jacob V
JV
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000098:blood supply; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D044022:Receptor, Endothelin A / Q000235:genetics*; D044023:Receptor, Endothelin B / Q000235:genetics*; D034421:Sus scrofa
D000701:Analgesics, Opioid; D019332:Endothelin-1; D009292:Narcotic Antagonists; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D009270:Naloxone; D009020:Morphine