Relationship between opioids and activation of phospholipase C and protein kinase C in brain injury induced pial artery vasoconstriction.
Previously, it has been observed that newborn pig pial artery constriction after fluid percussion brain injury was associated with elevated CSF dynorphin and beta endorphin concentration. Additionally, brain injury reversed dynorphin-induced pial artery vasodilation to vasoconstriction. The present study was designed to characterize the relationship between opioids and activation of phospholipase C (PLC) and protein kinase C (PKC) in brain injury-induced pial vasoconstriction. Anesthetized newborn pigs equipped with a closed cranial window were connected to a percussion device consisting of a saline-filled cylindrical reservoir with a metal pendulum. Brain injury of moderate severity (1.9-2.3 atm) was produced by allowing the pendulum to strike a piston on the cylinder. Brain injury decreased pial arteriolar diameter within 10 min of injury and continued to fall progressively for 3 h (130 +/- 5, 108 +/- 4 and 102 +/- 5 microns for 0, 10 and 180 min postinjury). In contrast, the PLC inhibitor, neomycin (10(-4) M), blunted brain injury-induced pial vasoconstriction (133 +/- 4, 129 +/- 4 and 135 +/- 5 microns for 0, 10 and 180 min postinjury, respectively). Similarly, staurosporine (10(-7) M), a PKC inhibitor, also blunted brain injury-induced vasoconstriction. beta endorphin (10(-8), 10(-6) M)-induced pial artery vasoconstriction was blunted by neomycin (12 +/- 1, 19 +/- 1 vs. 2 +/- 1, 4 +/- 2% constriction before and after neomycin, respectively). Staurosporine similarly blunted beta endorphin pial constriction (10 +/- 1, 15 +/- 1 vs. 1 +/- 1, 1 +/- 1% constriction before and after staurosporine, respectively). The constrictor potential for dynorphin was also inhibited by neomycin and staurosporine.(ABSTRACT TRUNCATED AT 250 WORDS)
Armstead
W M
WM
Department of Anesthesia, University of Pennsylvania, Philadelphia, USA.
D000818:Animals; D000831:Animals, Newborn; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000502:physiology; D001930:Brain Injuries / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D002536:Cerebral Arteries / Q000503:physiopathology; D004399:Dynorphins / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D008297:Male; D018847:Opioid Peptides / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013552:Swine; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014661:Vasoconstriction / Q000502:physiology*; D001615:beta-Endorphin / Q000378:metabolism
D018847:Opioid Peptides; D001615:beta-Endorphin; D004399:Dynorphins; D011493:Protein Kinase C; D010738:Type C Phospholipases