Sequential relationship between actions of CRF and PGE₂ in the brain on splenic sympathetic nerve activity in rats

An infusion of corticotropin-releasing factor (CRF, 0.1-5.0 μg/10 μl/rat) into the third cerebral ventricle (i.c.v.) for 10 min increased the splenic sympathetic nerve activity in a dose-dependent manner in urethane + α-chloralose anesthetized rats. No changes in the arterial blood pressure and body temperature were observed. The CRF (1.0 μg/10 μl)-induced enhancement of the splenic sympathetic nerve activity was completely blocked by an i.c.v. pretreatment with a CRF antagonist, α-helical CRF_9-41 (α-hCRF, 10 μg/10 μl). The increase in the splenic sympathetic nerve activity induced by CRF was not blocked by pretreatment with a cyclooxygenase inhibitor, sodium salicylate (100 μg/10 μl). In contrast, the splenic sympathetic nerve activity also increased after an i.c.v. injection of prostaglandin E₂ (PGE₂, 1 ng/10 μl) and the increase was completely blocked by i.c.v. pretreatment with α-hCRF. These findings suggested a sequential relationship between actions of CRF and PGE₂, with an activation of PGE₂ system followed by that of CRF system in the brain resulting in an increase in the splenic sympathetic nerve activity.