EP(1)-RECEPTOR MEDIATION OF PROSTAGLANDIN E(2)-INDUCED HYPERTHERMIA IN RATS

To investigate what type of prostanoid receptors are involved in the development of fever induced by brain prostaglandin E(2) (PGE(2)), PGE(2) and its analogues were injected into a lateral cerebroventricle (LCV) of rats, and the changes in colonic temperature (T-co) were observed in a 23 +/- 1 degrees C environment. 17-Phenyl-omega-trinor-PGE(2) (an EP(1) agonist; 0.01-10 nmol) produced a rapid and dose-dependent rise in T-co. Even though the EP(1) agonist was 10 times less potent than PGE(2) on a molar basis, the time course of this hyperthermia was quite similar to that of the PGE(2)-induced one. No fever was elicited by an LCV injection of butaprost (an EP(2) agonist; 0.1-100 nmol), 11-deoxy-PGE(1) (an EP(2) agonist; 0.1-1.0 nmol), or MB-28767 (an EP(3) agonist; 0.01-1.0 nmol). The PGE(2) (0.3 nmol)-induced hyperthermia was blocked by LCV pretreatment with SC-19220 (150 nmol), an EP(1) antagonist. The results suggest that the PGE(2)-induced hyperthermia in the rat is mediated predominantly through EP(1) receptors in the brain.