Endogenously generated 2-arachidonoylglycerol plays an inhibitory role in bombesin-induced activation of central adrenomedullary outflow in rats

Stimulatory and Inhibitory Roles of Brain 2-Arachidonoylglycerol in Bombesin-Induced Central Activation of Adrenomedullary Outflow in Rats

“…Actually, blockage of monoacylglycerol lipase activity by inhibitors or gene knockout resulted in increased 2-AG and decreased arachidonic acid levels in the mouse brain (38,39). Previously, we reported that central pretreatment with monoacylglycerol lipase inhibitor effectively reduced the centrally administered bombesin-induced elevation of plasma catecholamines in rats (16). These results suggest that brain arachidonic acid produced from 2-AG (as a precursor of prostanoids) is involved in the bombesin-induced response.…”

“…This 2-AGinduced retrograde signaling process seems to be involved in widespread effects, including synaptic plasticity (24), analgesia (25), neuroprotection and neurotoxicity (26,27), food intake (24,28), and also in the baroreflexevoked central sympathetic modulation (29). Recently, we reported that central pretreatment with AM 251 (an antagonist of cannabinoid CB 1 receptors) or AM 404 (an uptake-inhibitor of endocannabinoid) potentiated or reduced the centrally administered bombesin-induced elevation of plasma catecholamines, respectively (16). These results suggest that endogenously generated brain endocannabinoid (probably 2-AG) plays bidirectional roles (a stimulatory role as a precursor of prostanoids and an inhibitory role as an endocannabinoid) in the bombesin-induced elevation of plasma catecholamines in rats.…”

“…A phospholipase C (PLC)-mediated arachidonic acid producing pathway is also reported: 1) PLC cleaves the phosphodiester bond of membrane phospholipids, resulting in the formation of diacylglycerol (12); 2) diacylglycerol containing arachidonic acid in position 2 can be hydrolyzed to 2-arachidonoylglycerol (2-AG) by sn-1 selective diacylglycerol lipase (13); and 3) 2-AG can be further hydrolyzed by monoacylglycerol lipase to free arachidonic acid (14,15). Recently, using inhibitors of each lipase described above, we indirectly indicated the involvement of brain arachidonic acid generated by the brain PLC-, diacylglycerol lipase-, and monoacylglycerol lipase-mediated pathway in the bombesininduced responses in rats (11,16). Actually, this PLCmediated pathway has been reported to be a source of arachidonic acid from 2-AG in many cells such as bovine coronary endothelial cells (17), rabbit aorta (18), and murine melanoma cells (19).…”

“…Recently, we reported that centrally administered bombesin-induced elevation of plasma catecholamines was potentiated by central pretreatment with a cannabinoid CB 1 -receptor antagonist and was reduced by central pretreatment with an endocannabinoid uptake-inhibitor (16). These results suggest that brain endocannabinoid (probably 2-AG) acts on the bombesin-activated mechanisms, thereby inhibiting the bombesin-induced response through cannabinoid CB 1 receptor-mediated mechanisms in the brain, in addition to its stimulatory role as a precursor of brain prostanoids.…”

Possible inhibitory role of endogenous 2-arachidonoylglycerol as an endocannabinoid in (±)-epibatidine-induced activation of central adrenomedullary outflow in the rat

“…Brain 2-AG has been shown to inhibit neurotransmission through presynaptic CB 1 receptors (Di Marzo, 2006;Katona and Freund, 2012;Sugiura et al, 2006). We previously reported that CB 1 , but not CB 2 , receptors in the brain play an inhibitory role in the centrally administered each stress-related neuropeptide-(arginine-vasopressin, corticotropin-releasing factor (CRF) or bombesin) induced elevation of plasma catecholamines in the rat (Shimizu and Yokotani, 2008;Shimizu et al, 2010Shimizu et al, , 2011a. In the present study, therefore, we focused on CB 1 receptors.…”