Newborn pig nociceptin/orphanin FQ activates protein tyrosine kinase and mitogen activated protein kinase to impair NMDA cerebrovasodilation after ischemia.
This study characterized the contributions of protein tyrosine kinase and mitogen-activated protein kinase in nociceptin/orphanin FQ induced impairment of NMDA dilation after cerebral hypoxia/ischemia in anesthetized newborn pigs equipped with a closed cranial window. Topical nociceptin/orphanin FQ, in a concentration observed after hypoxia/ischemia, impaired NMDA pial artery vasodilation. Co-administration either of the protein tyrosine kinase inhibitor genistein or the mitogen activated protein kinase inhibitor U0126 with nociceptin/orphanin FQ partially prevented the inhibition of NMDA dilation compared to that observed in their absence. After exposure to hypoxia/ischemia, pial artery dilation in response to NMDA was reversed to vasoconstriction but pretreatment with either genistein or U0126 partially protected such impairment. These data show that protein tyrosine kinase and mitogen activated protein kinase activation contribute to nociceptin/orphanin FQ induced impairment of NMDA dilation. These data suggest that protein tyrosine and mitogen activated protein kinase are involved in the mechanism by which nociceptin/orphanin FQ impairs NMDA dilation following hypoxia/ischemia.
Philip
Shaji
S
Department of Anesthesia, University of Pennsylvania, Philadelphia 19104, USA.
Armstead
William M
WM
D000818:Animals; D000831:Animals, Newborn; D002545:Brain Ischemia / Q000201:enzymology*; D002536:Cerebral Arteries / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D020536:Enzyme Activators / Q000494:pharmacology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018847:Opioid Peptides / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D000097629:Nociceptin
D020536:Enzyme Activators; D020928:Mitogen-Activated Protein Kinases; D016202:N-Methylaspartate; D018847:Opioid Peptides; D011505:Protein-Tyrosine Kinases; D000097629:Nociceptin