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Differential activation of ERK, p38, and JNK MAPK by nociceptin/orphanin FQ in the potentiation of prostaglandin cerebrovasoconstriction after brain injury.

Abstract
Fluid percussion brain injury elevates the cerebrospinal fluid (CSF) concentration of the opioid nociceptin/orphanin FQ (N/OFQ), which potentiates vasoconstriction to the prostaglandins U 46619, a thromboxane A(2) mimic, and prostaglandin (PG)F(2a). This study investigated the role of the extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK) isoforms of mitogen activated protein kinase (MAPK) in potentiated prostaglandin vasoconstriction after brain injury and the relationship of brain injury induced release of N/OFQ to MAPK. Pial artery diameter was measured with a video microscaler by observation through a glass coverslip cranial window placed in the parietal cortex of newborn pigs. Brain injury potentiated U 46619 induced pial artery vasoconstriction but U 0126 and SB 203580 (10(-6) and 10(-5) M, respectively) (ERK and p38 MAPK inhibitors) blocked the potentiation. In contrast, administration of SP 600125 (10(-6) and 10(-5) M) (JNK MAPK inhibitor) only attenuated brain injury induced U 46619 potentiation and such responses were significantly different than that in the presence of either U 0126 or SB 203580 after FPI. Co-administration of N/OFQ (10(-10) M), the CSF concentration observed after brain injury, with U 46619 or PGF(2a) under non brain injury conditions potentiated prostaglandin vasoconstriction but U 0126 and SB 203580 blocked such potentiation. Administration of SP 600125 modestly attenuated prostaglandin potentiation by N/OFQ. These data show that activation of ERK and p38 primarily contribute to potentiation of prostaglandin constriction after brain injury. These data suggest that N/OFQ differentially activates ERK, p38, and JNK MAPK to contribute to potentiated prostaglandin vasoconstriction after fluid percussion brain injury.
AuthorsWilliam M Armstead
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 529 Issue 1-3 Pg. 129-35 (Jan 04 2006) ISSN: 0014-2999 [Print] Netherlands
PMID16352304 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Enzyme Inhibitors
  • Opioid Peptides
  • Prostaglandins
  • nociceptin
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
Topics
  • Animals
  • Brain Injuries (enzymology, physiopathology)
  • Cerebrovascular Circulation (drug effects, physiology)
  • Disease Models, Animal
  • Drug Interactions
  • Enzyme Activation
  • Enzyme Inhibitors (pharmacology)
  • Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors, metabolism)
  • Female
  • JNK Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
  • Male
  • Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
  • Opioid Peptides (cerebrospinal fluid, pharmacology)
  • Prostaglandins (pharmacology)
  • Swine
  • Vasoconstriction (drug effects, physiology)
  • p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)

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