Role of brain arachidonic acid cascade on central CRF 1 receptor-mediated activation of sympatho-adrenomedullary outflow in rats

Abstract

The present experiments were designed to characterize the mechanisms involved in the corticotropin releasing factor (CRF)-induced activation of central sympatho-adrenomedullary outflow in rats. Intracerebroventricularly (i.c.v.) administered CRF and urocortin (0.5, 1.5 and 3.0 nmol/animal) effectively and dose-dependently elevated plasma levels of adrenaline and noradrenaline, and the effect of urocortin was almost the same as that of CRF. The elevation of catecholamines induced by CRF and urocortin (1.5 nmol/animal) was reduced by CP-154,526(butyl-ethyl-{2,5-dimethyl-7-(2,4,6trimethylphenyl)-7 H-pyrrolo [2,3- d] pyrimidin-4-yl]amine), a selective CRF 1 receptor antagonist, in a dose dependent manner (1.2 and/or 2.4 μmol/animal, i.c.v.), and abolished by indomethacin (1.2 μmol/animal, i.c.v.), an inhibitor of cyclooxygenase. Furegrelate (1.8 μmol/animal, i.c.v.), an inhibitor of thromboxane A 2 synthase, abolished the CRF-induced elevation of adrenaline, but had no effect on the evoked release of noradrenaline. These results suggest that activation of brain CRF 1 receptor facilitates the central sympathetic and adrenomedullary outflow in distinct central pathways in rats: brain thromboxane A 2 is involved in the central adrenomedullary outflow; an active metabolite of arachidonic acid other than thromboxane A 2 (probably prostaglandin E 2) may be involved in the central sympathetic outflow.