TY - JOUR T1 - Orexin-A Activates Hypothalamic AMPK Signaling Through a Ca2+-dependent Mechanism Involving Voltage-gated L-type Calcium Channel JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.113.086744 SP - mol.113.086744 AU - Wen-Ning Wu AU - Peng-Fei Wu AU - Jun Zhou AU - Xin-Lei Guan AU - Zui Zhang AU - Yuan-Jian Yang AU - Li-Hong Long AU - Na Xie AU - Jian-Guo Chen AU - Fang Wang Y1 - 2013/01/01 UR - http://molpharm.aspetjournals.org/content/early/2013/09/25/mol.113.086744.abstract N2 - Hypothalamic AMP-activated protein kinase (AMPK) and orexins/hypocretins are both involved in the control of feeding behavior, but little is known about the interaction between these two signaling systems. Here, we demonstrated that orexin-A elicited significantly activation of AMPK in the arcuate nucleus (ARC) of hypothalamus by elevating [Ca2+]i involving extracellular calcium influx. Electrophysiological results revealed that orexin-A increased L-type calcium current via orexin receptor-phospholipase C-protein kinase C (OXR-PLC-PKC) signaling pathway in ARC neurons that produce neuropeptide Y (NPY), an important downstream effecter of orexin-A's orexigenic effect. Furthermore, L-type calcium channel inhibitor, nifedipine, attenuated orexin-A-induced AMPK activation in vitro and in vivo. We found that inhibition of AMPK by either compound C or the ATP mimetic 9-beta-D-arabinofuranoside (ara-A) prevented the appetite-stimulating effect of orexin-A. This action can be mimicked by nifedipine, the blocker of L-type calcium channel. Our results indicated that orexin-A activates hypothalamic AMPK signaling through a Ca2+-dependent mechanism involving voltage-gated L-type calcium channel, which may serve as a potential target for regulating feeding behavior. ER -