ROLES OF PROSTAGLANDINS D-2 AND E(2) IN INTERLEUKIN-1-INDUCED ACTIVATION OF NOREPINEPHRINE TURNOVER IN THE BRAIN AND PERIPHERAL ORGANS OF RATS

Possible roles of prostaglandins (PGs) in interleukin-l (Il-l)-induced activation of noradrenergic neurons were examined by assessing norepi nephrine (NE) turnover in the brain and peripheral organs of rats, An intraperitoneal injection of human recombinant IL-1 beta accelerated N E turnover in the hypothalamus, spleen, lung, diaphragm, and pancreas. A similar increase in NE turnover was also observed after intracerebr oventricular injection of corticotropin-releasing hormone (CRH), Pretr eatment with indomethacin (cyclooxygenase inhibitor) abolished the IL- 1-induced, but not the CRH-induced, increase in hypothalamic and splen ic NE turnover. To elucidate which eicosanoid-cyclooxygenase product(s ) is responsible for accelerating NE turnover, PGD(2), PGE(2), PGF(2 a lpha), U-46619 (stable thromboxane A(2) analogue), or carbacyclin (sta ble prostacyclin analogue) was administered intracerebroventricularly. Among them, PGE, was the only eicosanoid effective in increasing NE t urnover in spleen, whereas PGD(2) was effective in the hypothalamus. T he stimulative effect of PGD(2) was abolished by pretreatment with int racerebroventricular injection of a CRH antiserum. These results sugge st that the action of IL-1 is mediated through PGD, production to acti vate the noradrenergic neurons in the hypothalamus, and through PGE(2) production to increase sympathetic nerve activity in spleen.