Brain phospholipase C–diacylglycerol lipase pathway is involved in vasopressin-induced release of noradrenaline and adrenaline from adrenal medulla in rats

Abstract

Recently, we reported that intracerebroventricularly (i.c.v.) administered arginine–vasopressin evokes the release of noradrenaline and adrenaline from adrenal medulla by brain thromboxane A 2-mediated mechanisms in rats. These results suggest the involvement of brain arachidonic acid in the vasopressin-induced activation of the central adrenomedullary outflow. Arachidonic acid is released mainly by two pathways: phospholipase A 2 (PLA 2)-dependent pathway; phospholipase C (PLC)- and diacylglycerol lipase-dependent pathway. In the present study, therefore, we attempted to identify which pathway is involved in the vasopressin-induced release of both catecholamines from adrenal medulla using urethane-anesthetized rats. Vasopressin (0.2 nmol/animal, i.c.v.)-induced elevation of plasma noradrenaline and adrenaline was dose-dependently reduced by neomycin [0.28 and 0.55 μmol (250 and 500 μg)/animal, i.c.v.] and 1-[6-[[(17β)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1 H-pyrrole-2,5-dione (U-73122) [5 and 10 nmol (2.3 and 4.6 μg)/animal, i.c.v.] (inhibitors of PLC), and also by 1,6-bis(cyclohexyloximinocarbonylamino)hexane (RHC-80267) [1.3 and 2.6 μmol (500 and 1000 μg)/animal, i.c.v.] (an inhibitor of diacylglycerol lipase). On the other hand, mepacrine [1.1 and 2.2 μmol (500 and 1000 μg)/animal, i.c.v.] (an inhibitor of PLA 2) was largely ineffective on the vasopressin-induced elevation of plasma catecholamines. These results suggest that vasopressin evokes the release of noradrenaline and adrenaline from adrenal medulla by the brain PLC- and diacylglycerol lipase-dependent mechanisms in rats.