Basic Research
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Nov 7, 2008; 14(41): 6347-6354
Published online Nov 7, 2008. doi: 10.3748/wjg.14.6347
Leptin transiently antagonizes ghrelin and long-lastingly orexin in regulation of Ca2+ signaling in neuropeptide Y neurons of the arcuate nucleus
Daisuke Kohno, Shigetomo Suyama, Toshihiko Yada
Daisuke Kohno, Shigetomo Suyama, Toshihiko Yada, Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, Yakushiji 3311-1, Shimotsuke, Tochigi 329-0498, Japan
Author contributions: Kohno D mainly and Suyama S partly performed experiments; Yada T and Kohno D designed research and wrote the paper.
Supported by Grant-in-Aid for Scientific Research (B) (18390065, 20390061) and that on Priority Areas (15081101) from Japan Society for the Promotion of Science (JSPS), a grant from the 21st century Center of Excellence (COE) program, an Insulin Research Award from Novo Nordisk Pharma Ltd., a grant from Japan Diabetes Foundation, and a grant from the Smoking Research Foundation to TY
Correspondence to: Dr. Toshihiko Yada, Division of Integrative Physiology, Department of Physiology, Jichi Medical University, School of Medicine, Tochigi 329-0498, Japan. tyada@jichi.ac.jp
Telephone: +81-285-587320 Fax: +81-285-449962
Received: October 15, 2008
Revised: October 26, 2008
Accepted: November 2, 2008
Published online: November 7, 2008
Abstract

AIM: To explore the mechanism for interactions of leptin with ghrelin and orexin in the arcuate nucleus (ARC) activating neuropeptide Y (NPY) neurons during physiological regulation of feeding.

METHODS: Single neurons from ARC of adult rats with matured feeding function were isolated. [Ca2+]i was measured to monitore their activities. The time course of leptin effects on ghrelin-induced versus orexin-induced [Ca2+]i increases in NPY neurons was studied.

RESULTS: Administration of ghrelin or orexin-A at 10-10 mol/L increased cytosolic Ca2+ concentration ([Ca2+]i) in NPY neurons isolated from the ARC of adult rats. Upon administration of leptin at 10-14-10-12 mol/L, ghrelin-induced [Ca2+]i increases were initially (< 10 min) inhibited but later restored, exhibiting a transient pattern of inhibition. In contrast, orexin-induced [Ca2+]i increases were inhibited by leptin in a long-lasting manner. Furthermore, a prior administration of leptin inhibited orexin action but not ghrelin action to increase [Ca2+]i.

CONCLUSION: Leptin counteracted ghrelin effects transiently and orexin effects long-lastingly in NPY neurons. The transient property with which leptin counteracts ghrelin action in NPY neurons may allow the fasting-associated increase in ghrelin levels to activate NPY neurons in the presence of physiological leptin and to stimulate feeding.

Keywords: Leptin; Ghrelin; Orexin; Arcuate nucleus; Neuropeptide Y; Ca2+; Feeding; Phosphatidylinositol 3-kinase; Phosphodiesterase 3; Signal transducer and activator of transcription 3