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.
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The mechanisms by which cerebral ischemia occurs comprise morphological injury, hypotension in the presence of autoregulatory failure, inadequate availability of cholinergic neurotransmitters or nitric oxide, and potentiation of prostaglandin-induced vasoconstriction.
“The mechanisms by which cerebral ischemia occurs comprise morphological injury, such as vessel distortion as a result of mechanical displacement, hypotension in the presence of autoregulatory failure, inadequate availability of cholinergic neurotransmitters or nitric oxide, and potentiation of prostaglandin-induced vasoconstriction (112-115).”
From Pituitary Dysfunction After Traumatic Brain Injury: A Clinical and Pathophysiological Approach (2015) · cites this paper as [112]
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Nutrition in the Neurocritically Ill Patient
Overholt, B. L., & Badjatia, N. (2024) · Springer eBooks · doi:10.1007/978-3-031-62224-3_24
- Authors
- Armstead, W. M.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Armstead, William M.
- ORCID
- Armstead, William M.
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2006-01
- Volume
- 529
- Issue
- 1-3
- Pages
- 129-135
- ISSN
- 0014-2999 (ISSN-L)
- OpenAlex
- W2059386862
- Cited by
- 32
- References
- 30
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 4 · 2015: 4
- FWCI
- 0.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Psychiatry and Mental health › Migraine and Headache Studies
- Keywords
- nociceptin/orphanin FQ, ERK, p38 MAPK, JNK, MAPK signaling, fluid percussion injury, thromboxane A2, prostaglandin F2alpha, cerebrovascular response, MAPK inhibitors, newborn pigs
- MeSH terms
- Nociceptin, Animals, Brain Injuries, Cerebrovascular Circulation, Disease Models, Animal, Drug Interactions, Enzyme Activation, Enzyme Inhibitors, Female, Male, Prostaglandins, Swine, Vasoconstriction, Opioid Peptides, Mitogen-Activated Protein Kinases, JNK Mitogen-Activated Protein Kinases, Extracellular Signal-Regulated MAP Kinases, p38 Mitogen-Activated Protein Kinases
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