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Des-acyl Ghrelin Acts by CRF Type 2 Receptors to Disrupt Fasted Stomach Motility in Conscious Rats

https://doi.org/10.1053/j.gastro.2005.04.015Get rights and content

Background & Aims: Although it has been shown that des-acyl ghrelin decreases food intake and gastric emptying, no previous studies have examined the effects of des-acyl ghrelin on physiologic fed and fasted motor activity in the gastrointestinal tract. Methods: We examined the effects of intraperitoneal (IP) administration of des-acyl ghrelin on food intake and the effects of intracerebroventricular (ICV) or intravenous (IV) administration of des-acyl ghrelin on gastroduodenal motility using freely moving conscious rat models. The brain nuclei responding to these effects were examined by c-fos immunohistochemistry of the brain sections. Results: IP injection of des-acyl ghrelin decreased food intake, and this effect was not altered by capsaicin treatment. IP injection of des-acyl ghrelin enhanced c-fos expression in the arcuate and paraventricular nucleus but not in the nucleus of the solitary tract. Both ICV and IV injection of des-acyl ghrelin disrupted fasted motor activity in the antrum but not in the duodenum. Changes in gastric motility induced by IV injection of des-acyl ghrelin were completely antagonized by ICV injection of a selective corticotropin-releasing factor (CRF)2 receptor antagonist; however, the CRF1 receptor antagonist had no effects. Conclusions: The results suggest that des-acyl ghrelin decreases food intake and disrupts the fasted motor activity of the antrum in freely moving conscious rats. Peripheral des-acyl ghrelin may induce this function by direct activation of brain receptor by crossing the blood-brain barrier but not by the activation of vagal afferent pathways. In the brain, CRF2 receptor, but not CRF1 receptor, is involved in this action.

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Animals

Male Wistar rats (Clea Japan, Tokyo, Japan) weighing 230–280 g at the start of the experiment were used and housed in group cages under controlled illumination (light cycle, 8 am to 8 pm), humidity, and temperature (22.5°C ± 1.5°C) with free access to water and laboratory chow pellets (CE-2; Clea Japan). All experiments were performed between 9 am and 6 pm in fasted, freely moving conscious rats, in accordance with the Guide for Use of Experimental Animals of Shiga University of Medical

Effects of IP Injection of Des-acyl Ghrelin and Acylated Ghrelin on Food Intake in Food-Deprived and Free-Feeding Rats

The effects of des-acyl ghrelin and acylated ghrelin on food intake were examined in food-deprived and free-feeding rats. In 16-hour food-deprived rats, des-acyl ghrelin injected IP induced a significant decrease of 1-hour (4.15 ± 0.37 g) and 2-hour (4.42 ± 0.37 g) cumulative food intake compared with saline-injected controls (5.35 ± 0.30 g and 5.73 ± 0.32 g, respectively) (Figure 1A). On the other hand, acylated ghrelin injected IP induced a significant increase of 1-hour (6.25 ± 0.23 g) and

Discussion

In the present study, we first report the effects of des-acyl ghrelin on food intake and gastroduodenal motility in conscious rat models, and specific brain nuclei responding to these effects were examined compared with acylated ghrelin. In the food intake study, des-acyl ghrelin injected IP effectively decreased 1-hour and 2-hour cumulative food intake in food-deprived rats and also decreased the dark-phase food intake in free-feeding rats but failed to decrease the light-phase food intake in

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    Supported by a Grant-in-Aid (14571193) for Scientific Research from the Ministry of Education, Culture, Sports and Technology, Japan (to M.F.).

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