Ghrelin raises [Ca2+]i via AMPK in hypothalamic arcuate nucleus NPY neurons.
Ghrelin, an orexigenic hormone, directly activates neuropeptide (NPY) neurons in the hypothalamic arcuate nucleus (ARC), and thereby stimulates food intake. The hypothalamic level of AMP-activated protein kinase (AMPK), an intracellular energy sensor, is activated by peripheral and central administration of ghrelin. We examined whether ghrelin regulates AMPK activity in NPY neurons of the ARC. Single neurons were isolated from the ARC and cytosolic Ca(2+) concentration ([Ca(2+)](i)) was measured by fura-2 microfluorometry, followed by immunocytochemical identification of NPY, phospho-AMPK, and phospho-acetyl-CoA carboxylase (ACC). Ghrelin and AICAR, an AMPK activator, increased [Ca(2+)](i) in neurons isolated from the ARC. The ghrelin-responsive neurons highly overlapped with AICAR-responsive neurons. The neurons that responded to both ghrelin and AICAR were primarily NPY-immunoreactive neurons. Treatment with ghrelin increased phosphorylation of AMPK and ACC. An AMPK inhibitor, compound C, suppressed ghrelin-induced [Ca(2+)](i) increases. These results demonstrate that ghrelin increases [Ca(2+)](i) via AMPK-mediated signaling in the ARC NPY neurons.
Kohno
Daisuke
D
Division of Integrative Physiology, Department of Physiology, Jichi Medical University, School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
Sone
Hideyuki
H
Minokoshi
Yasuhiko
Y
Yada
Toshihiko
T
D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D054439:Ghrelin / Q000008:administration & dosage*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D054439:Ghrelin; D009478:Neuropeptide Y; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D002118:Calcium