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 (Tc) in a dose-dependent manner (1.6±0.1°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 Tc. ONO-AE-248 (20 nmol), an EP3 receptor agonist, also increased the Tc. However, the peak effect was delayed (1.2±0.2°C, 50 min after injection) compared to PGE2. In contrast, ONO-AE1-329, an EP4 receptor agonist, decreased the Tc. 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.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Clinical Neurology
- Developmental Biology