Central action of prostaglandin E2 and its methyl ester in the induction of hyperthermia after their systemic administration in urethane-anesthetized rats.

Intravenous injection of prostaglandin (PG) E2 (0.01-1.0 mg/kg) induced a dose-dependent increase in the rectal temperature of urethane-anesthetized rats; the maximum change attained was 0.14 +/- 0.08 to 1.38 +/- 0.16 degrees C at 23 to 51 min after injection. The i.v. injection of PGE2 methyl ester (PGE2-Me), a lipophilic derivative of PGE2, resulted in hyperthermia 1.5-fold higher than that by PGE2 injection over the same dose range. The hyperthermia was associated with tachycardia, hypertension, cutaneous vasodilation and a rise in abdominal skin temperature. Using [3H]PGE2 and radioimmunoassay, we showed PGE2 to be transported into the brain immediately (15 sec) after the i.v. injection of the PG; the PGE2 content ranged from 2.3 +/- 0.5 to 102.6 +/- 5.5 ng/g of brain when given at 0.01 to 1.0 mg/kg, which was 0.07 to 0.13% of the administered dose. When [3H]PGE2-Me was used, the radioactivity in the brain at 15 sec after injection was 1.3- to 2.9-fold higher than that after [3H]PGE2 injection. However, 80% or more of PGE2-Me was hydrolyzed rapidly and recovered as PGE2 in the brain within 15 sec post-injection. PGE2-Me disappeared within 5 min. When PGE2 or PGE2-Me administered i.v. was followed in terms of PGE2, it decreased gradually in the brain with a half-life of 9.0 to 9.5 min in both cases, and was almost undetectable (less than 0.7 ng/g of brain) at the time when rectal temperature reached a peak. The maximum change and duration of hyperthermia were correlated closely with the PGE2 content in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)