The EP and EP Receptor Subtypes both Mediate the Fever-producing Effects of Prostaglandin E in the Rostral Ventromedial Preoptic Area of the Hypothalamus in Rats.

This study aimed to re-examine the receptor subtype that mediates the fever-producing effects of prostaglandin E (PGE) in the rostral ventromedial preoptic area (rvmPOA) of the hypothalamus. Among the four subtypes of PGE receptors (EP, EP, EP, and EP), EP receptor is crucially involved in the febrile effects of PGE. However, it is possible for other subtypes of PGE receptor to contribute in the central mechanism of fever generation. Accordingly, effects of microinjection of PGE receptor subtype-specific agonists or antagonists were examined at the locus where a microinjection of a small amount (420 fmol) of PGE elicited prompt increases in the O consumption rate (VO), heart rate, and colonic temperature (T) in the rvmPOA of urethane-chloralose-anesthetized rats. The EP agonist sulprostone mimicked, whereas its antagonist L-798,106 reduced, the febrile effects of PGE microinjected into the same site. Similarly, the EP agonist rivenprost mimicked, whereas its antagonist ONO-AE3-208 reduced, the effects of PGE microinjected into the same site. In contrast, microinjection of the EP agonist iloprost induced a very small increase in VO but did not have significant influences on the heart rate and T, whereas its antagonist, AH6809, did not affect the PGE-induced responses. Microinjection of the EP agonist butaprost had no effects on the VO, heart rate, and T. The results suggest that the EP and EP receptor subtypes are both involved in the fever generated by PGE in the rvmPOA.