EP₁-receptor mediation of prostaglandin E₂-induced hyperthermia in rats

To investigate what type of prostanoid receptors are involved in the development of fever induced by brain prostaglandin E₂ (PGE₂), PGE₂ 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°C environment. 17-Phenyl-ω-trinor-PGE₂ (an EP₁ agonist; 0.01-10 nmol) produced a rapid and dose-dependent rise in T(co). Even though the EP₁ agonist was 10 times less potent than PGE₂ on a molar basis, the time course of this hyperthermia was quite similar to that of the PGE₂-induced one. No fever was elicited by an LCV injection of butaprost (an EP₂ agonist; 0.1- 100 nmol), 11-deoxy-PGE₁ (an EP₂ agonist; 0.1-1.0 nmol), or MB-28767 (an EP₃ agonist; 0.01-1.0 nmol). The PGE₂ (0.3 nmol)-induced hyperthermia was blocked by LCV pretreatment with SC-19220 (150 nmol), an EP₁ antagonist. The results suggest that the PGE₂-induced hyperthermia in the rat is mediated predominantly through EP₁ receptors in the brain.