COX-2 and mPGES in Brain Endothelial Cells: Potential Targets of Anti- Inflammatory Drugs

ISSN: 1875-614X (Online)
ISSN: 1871-5230 (Print)


Volume 15, 3 Issues, 2016


Download PDF Flyer




Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents

This journal supports open access

Aims & ScopeAbstracted/Indexed in


Submit Abstracts Online Submit Manuscripts Online

Editor-in-Chief:
Claudiu T. Supuran
Neurofarba Department
University of Florence
Florence
Italy


View Full Editorial Board

Subscribe Purchase Articles Order Reprints


COX-2 and mPGES in Brain Endothelial Cells: Potential Targets of Anti- Inflammatory Drugs



Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, 1(3): 161-166.

Author(s): K. Matsumura, K. Yamagata, T. Takemiya and S Kobayashi.

Affiliation: Department of Intelligence Science and Technology, Graduate School of Informatics, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan

Abstract

Prostaglandin E2 (PGE2) mediates fever and pain in various diseases through its action on the central nervous system (CNS). For the development of drugs that interfere with PGE2 action in the CNS, it is of importance to understand the nature of the PGE2 system there. Current studies on the PGE2 system in the CNS highlighted 2 groups of molecules on which drugs may act to interfere with the PGE2 action, i.e., (i) PGE2-synthesizing enzymes and (ii) PGE2 receptors. With respect to the first group, inducible-type cyclooxygenase (COX-2) and microsomal-type of PGE synthase (mPGES) were co-induced in CNS endothelial cells after systemic challenge with lipopolysaccharide or other inflammatory stimuli. Accumulating evidence has indicated that PGE2 produced through this endothelial COX-2-mPGES cascade is responsible for fever and pain. Of great importance is the fact that COX-2 and mPGES were co-induced preferentially in endothelial cells of the CNS and little in those of peripheral organs. Since drugs in the blood stream have quite effective access to the endothelial cells, it is theoretically possible to develop drugs that preferentially inhibit PGE2 synthesis in the CNS endothelial cells with lesser action on PGE2 synthesis in non-endothelial cells of peripheral organs, in which PGE2 might play housekeeping roles. Regarding the second group of potential drug targets, the EP3 subtype of PGE2 receptor is abundantly expressed in neurons of various brain regions including those involved in fever and pain modulation. However, in most of the brain regions, the pathophysiological roles of EP3 receptors are still unknown. Since EP3 receptors are expressed in parenchymal neurons, drugs that interfere with PGE2 at the receptor sites would need to pass through the blood-brain-barrier.

Keywords:

COX-2, Endothelial Cells, Anti- Inflammatory Drugs, EP3 receptors, blood-brain-barrier.



Purchase Online Order Reprints Order Eprints Rights and Permissions




Article Details

Volume: 1
Issue Number: 3
First Page: 161
Last Page: 166
Page Count: 6
DOI: 10.2174/1568014023355890
Price: $58
Advertisement

Related Journals




Webmaster Contact: urooj@benthamscience.org Copyright © 2016 Bentham Science