title: Relationship between opioids and activation of phospholipase C and protein kinase C in brain injury induced pial artery vasoconstriction.
abstract: 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)
authors.affiliation: Department of Anesthesia, University of Pennsylvania, Philadelphia, USA.
authors.forename: W M
authors.initials: WM
authors.lastname: Armstead
mesh_terms: 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
chemical_list: D018847:Opioid Peptides; D001615:beta-Endorphin; D004399:Dynorphins; D011493:Protein Kinase C; D010738:Type C Phospholipases