Contrasting effects of E type prostaglandin (EP) receptor agonists on core body temperature in rats.
Prostaglandin E2 (PGE2) is thought to be a principal fever mediator. There are four subtypes of PGE (EP) receptors, EP1-EP4. We investigated which EP receptors mediate PGE2-induced hyperthermia by injecting selective EP receptor agonists into the rat lateral cerebral ventricle under unrestrained condition. ONO-DI-004, an EP1 receptor agonist, increased the core temperature (T(c)) in a dose-dependent manner (1.6+/-0.1 degrees C at 20 nmol, with the peak 30 min after injection) with a time course similar to PGE2-induced hyperthermia. ONO-AE1-259-01 (20 nmol), an EP2 receptor agonist, did not change the T(c). ONO-AE-248 (20 nmol), an EP3 receptor agonist, also increased the T(c). However, the peak effect was delayed (1.2+/-0.2 degrees C, 50 min after injection) compared to PGE2. In contrast, ONO-AE1-329, an EP4 receptor agonist, decreased the T(c). These findings suggest that the EP1, EP3, and EP4 receptors all may contribute to the thermoregulatory response to PGE2, but each may have a different role.
Oka
Takakazu
T
Department of Neurology and Program in Neuroscience, Harvard Medical School, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02115, USA.
Oka
Kae
K
Saper
Clifford B
CB
D000818:Animals; D001831:Body Temperature / Q000187:drug effects* / Q000502:physiology; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006979:Hyperthermia, Induced; D007276:Injections, Intraventricular; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018078:Receptors, Prostaglandin E / Q000819:agonists* / Q000145:classification / Q000502:physiology
D008738:Methyl Ethers; C121546:ONO AE 248; C461399:ONO-AE1-329; D018078:Receptors, Prostaglandin E; D015232:Dinoprostone