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Cited by 386

The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.

Ghrelin Directly Interacts With Neuropeptide-Y-Containing Neurons in the Rat Arcuate Nucleus

Open access
Kohno, Daisuke, Gao, Hong-Zhi, Muroya, Shinji, Kikuyama, Sakae, Yada, Toshihiko·2003·Diabetes

Abstract

Ghrelin is a newly discovered peptide that is released from the stomach and from neurons in the hypothalamic arcuate nucleus (ARC) and potently stimulates growth hormone release and food intake. Neuropeptide-Y (NPY) neurons in the ARC play an important role in the stimulation of food intake. The present study aimed to determine whether ghrelin directly activates NPY neurons and, if so, to explore its signaling mechanisms. Whether the neurons that respond to ghrelin could be regulated by orexin and leptin was also examined. We isolated single neurons from the ARC of rats and measured the cytosolic Ca2+ concentration ([Ca2+]i) with fura-2 fluorescence imaging. Ghrelin (10−12 to 10−8 mol/l) concentration-dependently increased [Ca2+]i, which occurred in 35% of the ARC neurons. Approximately 80% of these ghrelin-responsive neurons were proved to be NPY-containing by immunocytochemical staining, and 58% of them were glucose-sensitive neurons as judged by their responses to lowering glucose concentrations. The [Ca2+]i responses to ghrelin were markedly attenuated by inhibitors of protein kinase A (PKA) but not protein kinase C and by a blocker of N-type but not L-type Ca2+ channels. Orexin increased [Ca2+]i and leptin attenuated ghrelin-induced [Ca2+]i increases in the majority (80%) of ghrelin-responsive NPY neurons. These results demonstrate that ghrelin directly interacts with NPY neurons in the ARC to induce Ca2+ signaling via PKA and N-type Ca2+ channel-dependent mechanisms. The integration of stimulatory effects of ghrelin and orexin and inhibitory effect of leptin may play an important role in the regulation of the activity of NPY neurons and thereby feeding.

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Metadata

Authors
Kohno, D., Gao, H.-Z., Muroya, S., Kikuyama, S., & Yada, T.
Venue
Diabetes
Published
2003-04-01
Volume
52
Issue
4
Pages
948-956
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
OpenAlex
W2120228339
Cited by
386
References
41
FWCI
8.63
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Ghrelin Directly Interacts With Neuropeptide-Y-Containing Neurons in the Rat Arcuate Nucleus. https://app.cochat.ai/papers/10.2337/diabetes.52.4.948
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Kohno, D., Gao, H.-Z., Muroya, S., Kikuyama, S., & Yada, T. (2003). Ghrelin Directly Interacts With Neuropeptide-Y-Containing Neurons in the Rat Arcuate Nucleus. Diabetes. https://doi.org/10.2337/diabetes.52.4.948

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