Roles of prostaglandins D2 and E2 in interleukin-1-induced activation of norepinephrine turnover in the brain and peripheral organs of rats.
Possible roles of prostaglandins (PGs) in interleukin-1 (IL-1)-induced activation of noradrenergic neurons were examined by assessing norepinephrine (NE) turnover in the brain and peripheral organs of rats. An intraperitoneal injection of human recombinant IL-1 beta accelerated NE turnover in the hypothalamus, spleen, lung, diaphragm, and pancreas. A similar increase in NE turnover was also observed after intracerebroventricular injection of corticotropin-releasing hormone (CRH). Pretreatment with indomethacin (cyclooxygenase inhibitor) abolished the IL-1-induced, but not the CRH-induced, increase in hypothalamic and splenic NE turnover. To elucidate which eicosanoid-cyclooxygenase product(s) is responsible for accelerating NE turnover, PGD2, PGE2, PGF2 alpha, U-46619 (stable thromboxane A2 analogue), or carbacyclin (stable prostacyclin analogue) was administered intracerebroventricularly. Among them, PGE2 was the only eicosanoid effective in increasing NE turnover in spleen, whereas PGD2 was effective in the hypothalamus. The stimulative effect of PGD2 was abolished by pretreatment with intracerebroventricular injection of a CRH antiserum. These results suggest that the action of IL-1 is mediated through PGD2 production to activate the noradrenergic neurons in the hypothalamus, and through PGE2 production to increase sympathetic nerve activity in spleen.
Terao
A
A
Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Kitamura
H
H
Asano
A
A
Kobayashi
M
M
Saito
M
M
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000276:immunology / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D005260:Female; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D013154:Spleen / Q000294:innervation*
D007375:Interleukin-1; D011994:Recombinant Proteins; D003346:Corticotropin-Releasing Hormone; D015232:Dinoprostone; D015230:Prostaglandin D2; D009638:Norepinephrine; D007213:Indomethacin