The Orexigenic Effect of Ghrelin Is Mediated through Central Activation of the Endogenous Cannabinoid System
Figure 4
Schematic drawing illustrates the proposed model of ghrelin's action in the parvocellular neurons of the PVN.
Binding of ghrelin to its receptor (growth hormone secretagogue receptor 1a, GHS-R1a) on the surface of parvocellular neurons results in an increase of intracellular Ca2+ levels due to mobilization of Ca2+ from intracellular stores and opening Ca2+ channels. The increased intracellular Ca2+ level activates the 2-AG synthesizing enzyme diacylglycerol lipase-α (DAGL), directly or through activation of protein kinase C (PKC), resulting in an increased 2-AG synthesis and release into the extracellular space. The increased activation of presynaptic CB1 then inhibits the release of the excitatory neurotransmitter glutamate (Glu) from the axons innervating the PVN neurons. Intracellular administration of the Ca2+-chelator BAPTA blocks this cascade by preventing the increase of intracellular Ca2+ level, whereas extracellularly-given THL blocks the 2-AG synthesis and AM251 blocks the cascade at the level of CB1.