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Intracerebroventricular urocortin 3 counteracts central acyl ghrelin-induced hyperphagic and gastroprokinetic effects via CRF receptor 2 in rats

PURPOSE: Urocortin 3 is a key neuromodulator in the regulation of stress, anxiety, food intake, gut motility, and energy homeostasis, while ghrelin elicits feeding behavior and enhances gastric emptying, adiposity, and positive energy balance. However, the interplays between urocortin 3 and ghrelin...

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Autores principales: Yeh, Chun, Ting, Ching-Heng, Doong, Ming-Luen, Chi, Chin-Wen, Lee, Shou-Dong, Chen, Chih-Yen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5055120/
https://www.ncbi.nlm.nih.gov/pubmed/27757017
http://dx.doi.org/10.2147/DDDT.S113195
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author Yeh, Chun
Ting, Ching-Heng
Doong, Ming-Luen
Chi, Chin-Wen
Lee, Shou-Dong
Chen, Chih-Yen
author_facet Yeh, Chun
Ting, Ching-Heng
Doong, Ming-Luen
Chi, Chin-Wen
Lee, Shou-Dong
Chen, Chih-Yen
author_sort Yeh, Chun
collection PubMed
description PURPOSE: Urocortin 3 is a key neuromodulator in the regulation of stress, anxiety, food intake, gut motility, and energy homeostasis, while ghrelin elicits feeding behavior and enhances gastric emptying, adiposity, and positive energy balance. However, the interplays between urocortin 3 and ghrelin on food intake and gastric emptying remain uninvestigated. METHODS: We examined the differential effects of central O-n-octanoylated ghrelin, des-Gln(14)-ghrelin, and urocortin 3 on food intake, as well as on charcoal nonnutrient semiliquid gastric emptying in conscious rats that were chronically implanted with intracerebroventricular (ICV) catheters. The functional importance of corticotropin-releasing factor (CRF) receptor 2 in urocortin 3-induced responses was examined by ICV injection of the selective CRF receptor 2 antagonist, astressin(2)-B. RESULTS: ICV infusion of urocortin 3 opposed central acyl ghrelin-elicited hyperphagia via CRF receptor 2 in satiated rats. ICV injection of O-n-octanoylated ghrelin and des-Gln(14)-ghrelin were equally potent in accelerating gastric emptying in fasted rats, whereas ICV administration of urocortin 3 delayed gastric emptying. In addition, ICV infusion of urocortin 3 counteracted central acyl ghrelin-induced gastroprokinetic effects via CRF receptor 2 pathway. CONCLUSION: ICV-infused urocortin 3 counteracts central acyl ghrelin-induced hyperphagic and gastroprokinetic effects via CRF receptor 2 in rats. Our results clearly showed that enhancing ghrelin and blocking CRF receptor 2 signaling in the brain accelerated gastric emptying, which provided important clues for a new therapeutic avenue in ameliorating anorexia and gastric ileus found in various chronic wasting disorders.
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spelling pubmed-50551202016-10-18 Intracerebroventricular urocortin 3 counteracts central acyl ghrelin-induced hyperphagic and gastroprokinetic effects via CRF receptor 2 in rats Yeh, Chun Ting, Ching-Heng Doong, Ming-Luen Chi, Chin-Wen Lee, Shou-Dong Chen, Chih-Yen Drug Des Devel Ther Original Research PURPOSE: Urocortin 3 is a key neuromodulator in the regulation of stress, anxiety, food intake, gut motility, and energy homeostasis, while ghrelin elicits feeding behavior and enhances gastric emptying, adiposity, and positive energy balance. However, the interplays between urocortin 3 and ghrelin on food intake and gastric emptying remain uninvestigated. METHODS: We examined the differential effects of central O-n-octanoylated ghrelin, des-Gln(14)-ghrelin, and urocortin 3 on food intake, as well as on charcoal nonnutrient semiliquid gastric emptying in conscious rats that were chronically implanted with intracerebroventricular (ICV) catheters. The functional importance of corticotropin-releasing factor (CRF) receptor 2 in urocortin 3-induced responses was examined by ICV injection of the selective CRF receptor 2 antagonist, astressin(2)-B. RESULTS: ICV infusion of urocortin 3 opposed central acyl ghrelin-elicited hyperphagia via CRF receptor 2 in satiated rats. ICV injection of O-n-octanoylated ghrelin and des-Gln(14)-ghrelin were equally potent in accelerating gastric emptying in fasted rats, whereas ICV administration of urocortin 3 delayed gastric emptying. In addition, ICV infusion of urocortin 3 counteracted central acyl ghrelin-induced gastroprokinetic effects via CRF receptor 2 pathway. CONCLUSION: ICV-infused urocortin 3 counteracts central acyl ghrelin-induced hyperphagic and gastroprokinetic effects via CRF receptor 2 in rats. Our results clearly showed that enhancing ghrelin and blocking CRF receptor 2 signaling in the brain accelerated gastric emptying, which provided important clues for a new therapeutic avenue in ameliorating anorexia and gastric ileus found in various chronic wasting disorders. Dove Medical Press 2016-10-03 /pmc/articles/PMC5055120/ /pubmed/27757017 http://dx.doi.org/10.2147/DDDT.S113195 Text en © 2016 Yeh et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Yeh, Chun
Ting, Ching-Heng
Doong, Ming-Luen
Chi, Chin-Wen
Lee, Shou-Dong
Chen, Chih-Yen
Intracerebroventricular urocortin 3 counteracts central acyl ghrelin-induced hyperphagic and gastroprokinetic effects via CRF receptor 2 in rats
title Intracerebroventricular urocortin 3 counteracts central acyl ghrelin-induced hyperphagic and gastroprokinetic effects via CRF receptor 2 in rats
title_full Intracerebroventricular urocortin 3 counteracts central acyl ghrelin-induced hyperphagic and gastroprokinetic effects via CRF receptor 2 in rats
title_fullStr Intracerebroventricular urocortin 3 counteracts central acyl ghrelin-induced hyperphagic and gastroprokinetic effects via CRF receptor 2 in rats
title_full_unstemmed Intracerebroventricular urocortin 3 counteracts central acyl ghrelin-induced hyperphagic and gastroprokinetic effects via CRF receptor 2 in rats
title_short Intracerebroventricular urocortin 3 counteracts central acyl ghrelin-induced hyperphagic and gastroprokinetic effects via CRF receptor 2 in rats
title_sort intracerebroventricular urocortin 3 counteracts central acyl ghrelin-induced hyperphagic and gastroprokinetic effects via crf receptor 2 in rats
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5055120/
https://www.ncbi.nlm.nih.gov/pubmed/27757017
http://dx.doi.org/10.2147/DDDT.S113195
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