Role of brain arachidonic acid cascade on central CRF1 receptor-mediated activation of sympatho-adrenomedullary outflow in rats.
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)-7H-pyrrolo [2,3-d] pyrimidin-4-yl]amine), a selective CRF1 receptor antagonist, in a dose dependent manner (1.2 and/or 2.4 micromol/animal, i.c.v.), and abolished by indomethacin (1.2 micromol/animal, i.c.v.), an inhibitor of cyclooxygenase. Furegrelate (1.8 micromol/animal, i.c.v.), an inhibitor of thromboxane A2 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 CRF1 receptor facilitates the central sympathetic and adrenomedullary outflow in distinct central pathways in rats; brain thromboxane A2 is involved in the central adrenomedullary outflow; an active metabolite of arachidonic acid other than thromboxane A2 (probably prostaglandin E2) may be involved in the central sympathetic outflow.
Yokotani
K
K
Department of Pharmacology, Kochi Medical School, Japan. yokotani@dtn.am400gw.kochi-ms.ac.jp
Murakami
Y
Y
Okada
S
S
Hirata
M
M
D000704:Analysis of Variance; D000818:Animals; D016718:Arachidonic Acid / Q000502:physiology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology* / Q000502:physiology*; D004837:Epinephrine / Q000097:blood*; D007276:Injections, Intraventricular; D008297:Male; D009638:Norepinephrine / Q000097:blood*; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000187:drug effects*; D054832:Urocortins
C101628:CP 154526; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D016718:Arachidonic Acid; D003346:Corticotropin-Releasing Hormone; D009638:Norepinephrine; D004837:Epinephrine