Daisuke Kohno1, Shigetomo Suyama, Toshihiko Yada. 1. Division of Integrative Physiology, Department of Physiology, Jichi Medical University, School of Medicine, Tochigi 329-0498, Japan.
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 monitor 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.
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 monitor 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.
Authors: Y Date; Y Ueta; H Yamashita; H Yamaguchi; S Matsukura; K Kangawa; T Sakurai; M Yanagisawa; M Nakazato Journal: Proc Natl Acad Sci U S A Date: 1999-01-19 Impact factor: 11.205
Authors: T Sakurai; A Amemiya; M Ishii; I Matsuzaki; R M Chemelli; H Tanaka; S C Williams; J A Richardson; G P Kozlowski; S Wilson; J R Arch; R E Buckingham; A C Haynes; S A Carr; R S Annan; D E McNulty; W S Liu; J A Terrett; N A Elshourbagy; D J Bergsma; M Yanagisawa Journal: Cell Date: 1998-02-20 Impact factor: 41.582
Authors: R M Chemelli; J T Willie; C M Sinton; J K Elmquist; T Scammell; C Lee; J A Richardson; S C Williams; Y Xiong; Y Kisanuki; T E Fitch; M Nakazato; R E Hammer; C B Saper; M Yanagisawa Journal: Cell Date: 1999-08-20 Impact factor: 41.582