IMR Press / FBL / Volume 9 / Issue 5 / DOI: 10.2741/1458

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

Prostaglandin E2 as a mediator of fever: the role of prostaglandin E (EP) receptors

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1 Division of Psychosomatic Medicine, Department of Neurology, University of Occupational and Environmental Health, Japan
Academic Editor:Andrej Romanovsky
Front. Biosci. (Landmark Ed) 2004, 9(5), 3046–3057; https://doi.org/10.2741/1458
Published: 1 September 2004
(This article belongs to the Special Issue Fever and hypothermia in systemic Inflammation)
Abstract

Prostaglandin E2 (PGE2) is a principal fever mediator that induces hyperthermia when injected into the organum vasculosum lamina terminalis (OVLT) and the adjacent preoptic area of the hypothalamus (POA). PGE (EP) receptors have four subtypes, i.e. EP1, EP2, EP3, and EP4. In the rat OVLT/POA region, at least three of these receptors, i.e. EP1, EP3, and EP4 receptors, have distinctively different distribution patterns. In rats, intracerebroventricular injection of EP1 receptor agonists and EP3 receptor agonists increased core temperature (Tc) and that of an EP4 receptor agonist decreased it. IntraPOA injection of an EP1 receptor agonist increased Tc. IntraPOA injection of an EP3 receptor agonist, however, induced hyperalgesia but not hyperthermia. Studies using mice with EP receptor gene deletions have indicated that EP3 receptors play a crucial role in febrile response. Therefore, the involvement of EP3 receptors at other levels of the nervous system should be considered. Such nuclei include the raphe pallidus nucleus, intermediolateral cell column in the spinal cord, or the nucleus of the solitary tract.

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