Brain phospholipase C and diacylglycerol lipase are involved in corticotropin-releasing hormone-induced sympatho-adrenomedullary outflow in rats

Abstract

Previously, we reported that the elevation of plasma noradrenaline and adrenaline induced by intracerebroventricularly (i.c.v.) administered corticotropin-releasing hormone (CRH) was abolished by i.c.v. administered indomethacin, an inhibitor of cyclooxygenase, in rats [Yokotani et al., Eur. J. Pharmacol. 419, 183-189, 2001]. The result suggests the involvement of active metabolites of brain arachidonic acid in the CRH-induced activation of the central sympatho-adrenomedullary outflow. Arachidonic acid is released mainly by two different pathways: phospholipase A 2-dependent pathway; phospholipase C- and diacylglycerol lipase-dependent pathway. In the present study, therefore, we tried to identify which pathway is involved in the CRH-induced elevation of plasma catecholamines in urethane-anesthetized rats. CRH (1.5 nmol/animal, i.c.v.)-induced elevation of plasma noradrenaline and adrenaline was abolished by neomycin [0.55 μmol (500 μg)/animal, i.c.v.] and 1-(6-((17β-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U-73122) [5 nmol (2.3 μg)/animal, i.c.v.] (inhibitors of phospholipase C), and also by 1,6-bis-(cyclohexyloximinocarbonylamino)-hexane (RHC-80267) [1.3 μmol (500 μg)/animal, i.c.v.] (an inhibitor of diacylglycerol lipase). On the other hand, mepacrine [1.1 μmol (500 μg)/animal, i.c.v.] (an inhibitor of phospholipase A 2) and 1-(6-((17β-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-2,5-pyrrolidinedione (U-73343) [5 nmol (2.3 μg)/animal, i.c.v.] (an inactive analog of U-73122) had no effect. These results suggest that CRH activates the central sympatho-adrenomedullary outflow by the brain phospholipase C- and diacylglycerol lipase-dependent mechanisms in rats.