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Published on: September 18, 2014
Mechanism of delayed gastric emptying in naturally occurring CCK-A receptor gene knockout (OLETF) rats
1Department of Clinical Physiology, Tokyo Metropolitan Institute of Gerontology, Tokyo, 173-0015 Japan.
Abstract:
We recently found a specific strain of rats (OLETF rats) in which CCK-A receptor gene expression is lacking because of a genetic abnormality. As delayed gastric emptying has been reported in this strain, we examined its mechanism. A liquid gastric load containing phenol red was administered using an orogastric tube into the stomach in OLETF and control (LETO) rats. The stomach was removed 0, 15, 30 and 45 min after meal ingestion and the content of phenol red was measured to estimate the rate of gastric emptying. Pretreatment of reserpine enhanced gastric emptying in both strains. A tenfold dose of reserpine was required in OLETF rats to induce a similar effect to LETO rats. The plasma noradrenalin level was significantly higher in OLETF than LETO rats. When the smooth muscle of the stomach was isolated and contraction in vitro was examined, the smooth muscle functions were not deteriorated in OLETF rats. The thickness of muscle determined by hematoxylin-eosin staining was not different between strains. It is suggested that the delayed gastric emptying in OLETF rats may be due to increased sympathetic nerve function.
Insights
Obesity-prone OLETF rats exhibit delayed gastric emptying due to increased sympathetic nerve activity, not impaired stomach muscle function. This suggests a novel mechanism for slowed digestion in these rats.
Area of Science:
- Physiology
- Gastroenterology
- Endocrinology
Background:
- Obesity-prone OLETF rats genetically lack CCK-A receptor expression.
- These rats exhibit delayed gastric emptying, but the underlying mechanism is unclear.
Purpose of the Study:
- To investigate the mechanism of delayed gastric emptying in OLETF rats.
- To determine if impaired stomach smooth muscle function or altered nerve activity contributes to delayed gastric emptying.
Main Methods:
- Gastric emptying was assessed in OLETF and control LETO rats using a phenol red liquid meal.
- Reserpine was administered to evaluate its effect on gastric emptying in both rat strains.
- Plasma noradrenaline levels were measured.
- In vitro stomach smooth muscle contractility and muscle thickness were examined.
Main Results:
- OLETF rats showed significantly delayed gastric emptying compared to LETO rats.
- Higher doses of reserpine were needed to enhance gastric emptying in OLETF rats.
- Plasma noradrenaline levels were elevated in OLETF rats.
- Stomach smooth muscle function and thickness were comparable between OLETF and LETO rats.
Conclusions:
- Delayed gastric emptying in OLETF rats is not due to impaired stomach smooth muscle function.
- Increased sympathetic nerve function, indicated by higher plasma noradrenaline, is suggested as the cause of delayed gastric emptying in OLETF rats.
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