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

Abstract

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-Gln¹⁴-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, astressin₂-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-Gln¹⁴-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.

Keywords:

• corticotropin-releasing factor receptor
• des-Gln¹⁴-ghrelin
• food intake
• gastric emptying
• intracerebroventricular
• urocortin 3

Acknowledgments

This project was funded by grants from Taiwan Ministry of Science and Technology (NSC 97-2314-B-010-024-MY2 to C-YC) and in part supported by a grant from the Cheng Hsin General Hospital (103F003C13 to S-DL and C-YC). We would like to thank Miss Yu-chi Lee for her secretarial assistance in editing this manuscript, as well as the Clinical Research Core Laboratory of Taipei Veterans General Hospital for providing experimental space and facilities.

Authors contributions

CY, C-HT, M-LD, and S-DL participated in the conception, design, and acquisition of data of the research. C-WC and C-YC wrote and revised the paper. All authors contributed toward data analysis, drafting and revising the paper and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.