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Eur J Pharmacol. 2006 Jan 4;529(1-3):129-35. Epub 2005 Dec 13.

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

Author information

1
Department of Anesthesiology and Critical Care Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. armsteaw@uphs.upenn.edu

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.

PMID:
16352304
DOI:
10.1016/j.ejphar.2005.08.059
[Indexed for MEDLINE]

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