Biochemical changes in prostanoids and cerebral expression of cyclooxygenase (COX)-1 and COX-2 during morphine sulfate infusion in the newborn piglet .
To examine the biochemical regulation of morphine sulfate (MS) on prostanoid synthesis, conscious newborn piglets received a bolus dose of 100 microg/kg followed by a continuous infusion dose of 100 microg/kg/h. The control group received equivalent volume bolus and continuous infusion of 5% dextrose. Blood samples were drawn from the femoral artery and sagittal sinus vein before, during and after infusion for measurement of prostanoids. The expression of mRNAs encoding cyclooxygenases (COX)-1 and -2 in the brainstem, thalamus, cortex, and cerebellum of the newborn piglets were also examined. Systemic PGE2 levels declined substantially during and post MS infusion (p < 0.01), whereas sagittal sinus vein PGE2 levels increased following the bolus dose (p < 0.01) and at 4 h of continuous infusion (p < 0.01). MS infusion did not affect systemic 6-ketoPGF1alpha levels, however, in the cerebral circulation 6-ketoPGF1alpha levels increased 146% (p < 0.01) following the bolus dose and remained elevated throughout the infusion and post infusion times. Systemic TxB2 levels increased transiently at 4 h (p < 0.01) and sagittal sinus vein TxB2 increased at 0.5 and 1 h (p < 0.01) during continuous infusion. RT-PCR assays revealed a 1.5- (p < 0.001) to 4-fold (p < 0.001) increased expression of COX-1 mRNA in the MS-infused brain samples. In contrast, no differences in COX-2 mRNA were detected between the groups. These data imply that MS may have significant effects on prostanoid synthesis in the newborn. The data further show that the MS-induced prostanoid responses appear to be mediated via COX-1.
Tumbaga
P
P
Department of Pediatrics, University of California, Irvine Medical Center, Orange 92868, USA.
Beharry
K
K
Akmal
Y
Y
Federico
C
C
Modanlou
H D
HD
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001921:Brain / Q000201:enzymology*; D001923:Brain Chemistry; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D006439:Hemodynamics / Q000187:drug effects; D007527:Isoenzymes / Q000187:drug effects* / Q000235:genetics; D009020:Morphine / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects* / Q000235:genetics; D011453:Prostaglandins / Q000097:blood*; D012333:RNA, Messenger / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine
D000701:Analgesics, Opioid; D007527:Isoenzymes; D011453:Prostaglandins; D012333:RNA, Messenger; D009020:Morphine; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases