Hypothalamic 11,12-epoxyeicosatrienoic acid attenuates fever induced by central interleukin-1beta in the rat.
Inhibitors of cytochrome P-450 augment fever in rats and mice, indicating that the metabolite of the enzyme is candidate of endogenous antipyretic. Cytochrome P-450 of arachidonic acid cascade leads to the formation of regioisomeric 5,6-, 8,9- 11,12- and 14,15-epoxyeicosatrienoic acid (EET). Various isomers of EET were administrated into the preoptic area and anterior hypothalamus (PO/AH) to test their influence on fever induced by interleukin-1beta (IL-1beta) administrated into the PO/AH in conscious rats. The IL-beta-induced fever was attenuated in the 11,12-EET-pretreated rats, although 5,6-, 8,9- and 14,15-EET did not affect the fever. Intra-PO/AH injection of 11,12-EET did not alter normal body temperature. The results suggest that 11,12-EET acts in the hypothalamus as an endogenous antipyretic.
Nakashima
T
T
Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan. nakasima@ipc.kit.ac.jp
Yoshida
Y
Y
Miyata
S
S
Kiyohara
T
T
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000378:metabolism*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D007025:Anterior Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005334:Fever / Q000139:chemically induced / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D011301:Preoptic Area / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
D018712:Analgesics, Non-Narcotic; D007375:Interleukin-1; D014665:Vasodilator Agents; D016718:Arachidonic Acid; C046783:11,12-epoxy-5,8,14-eicosatrienoic acid; D003577:Cytochrome P-450 Enzyme System; D015126:8,11,14-Eicosatrienoic Acid