Protease-activated receptor-2 regulates trypsin expression in the brain and protects against seizures and epileptogenesis
| Autor: | Thomas M. Cocks, Terence J. O'Brien, Rink-Jan Lohman |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Agonist
Proteases Tissue plasminogen activator (tPA) medicine.drug_class Proteolysis medicine.medical_treatment Hippocampus Biology Epileptogenesis lcsh:RC321-571 Seizures medicine Animals Receptor PAR-2 Trypsin Rats Wistar Evoked Potentials lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Protease-activated receptor 2 Neurons Analysis of Variance Protease medicine.diagnostic_test Brain Dose-Response Relationship Radiation Electroencephalography Protease-activated receptor-2 (PAR2) Amygdala Electric Stimulation Electrodes Implanted Rats Cell biology SLIGRL Gene Expression Regulation nervous system Neurology Female Oligopeptides Neuroscience medicine.drug |
| Zdroj: | Neurobiology of Disease, Vol 30, Iss 1, Pp 84-93 (2008) |
| ISSN: | 0969-9961 |
| DOI: | 10.1016/j.nbd.2007.12.010 |
| Popis: | Protease-activated receptor-2 (PAR(2)), primarily involved in inflammation, is highly expressed in limbic regions of the brain such as the hippocampus. Although extracellular proteolysis is involved in normal and stress-related neuronal plasticity associated with learning, memory and inflammatory disease states, little is known about the role of PAR(2) and its physiological agonist, trypsin, in the brain. We show immunohistochemically that trypsin co-localises with tissue plasminogen activator within granular-like structures in PAR(2)-positive pyramidal neurons of the rat hippocampus. Central administration of the PAR(2) peptide agonist, SLIGRL, inhibited electrical amygdala kindling-induced epileptogenesis and abolished kindling-induced over-expression of trypsin in the hippocampus. SLIGRL similarly attenuated kindling when administered subcutaneously. Non-enzymatic activation of neuronal PAR(2) using SLIGRL may thus activate feedback mechanisms to inhibit the over-production of trypsin and possibly other proteases during brain insults and thereby attenuate pathogenesis. Prophylactic systemic administration of non-proteolytic PAR(2) agonists may therefore represent a novel approach to protect against epileptogenic brain insults. |
| Databáze: | OpenAIRE |
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