Mechanism of delayed gastric emptying in naturally occurring CCK-A receptor gene knockout (OLETF) rats

M Ohta1, S Kanai, Y Sato

  • 1Department of Clinical Physiology, Tokyo Metropolitan Institute of Gerontology, Tokyo, 173-0015 Japan.

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.

Related Concept Videos

Hormonal Regulation01:40

Hormonal Regulation

Hormones regulate a significant portion of digestion through activation of the neuroendocrine system. The neuroendocrine system of digestion contains many different hormones all with multiple functions that are both, directly and indirectly, involved in digestion.
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Intestinal Phase of Digestion01:29

Intestinal Phase of Digestion

The intestinal phase of digestion is the third and final stage of the digestive process, occurring after the cephalic and gastric phases. It begins when chyme, a partially digested mixture of food and digestive enzymes, enters the small intestine from the stomach. This phase is crucial for nutrient absorption and involves complex hormonal and enzymatic interactions.
The arrival of the chyme in the small intestine distends the duodenum, which triggers the enterogastric reflex. This distension...
Gastric Motility01:16

Gastric Motility

Gastric motility is the coordinated contraction and relaxation of stomach muscles that convert ingested food into chyme, a semi-liquid substance ready for further digestion in the intestines. The process begins with the vagus nerve inducing the relaxation of the smooth muscles in the fundus and body of the stomach, allowing these regions to expand and accommodate up to approximately 1.5 liters of food and liquid.
Peristaltic Waves and Chyme Formation
Upon food entry, the stomach initiates...
Gastric Emptying01:16

Gastric Emptying

Gastric emptying occurs when the stomach gradually releases chyme into the duodenum. When the stomach is distended, it triggers the release of gastrin, a hormone that promotes gastric acid secretion to aid in digestion. Additionally, stomach distension contributes to peristaltic waves that propel gastric contents toward the pyloric region. The gastroenteric reflex, on the other hand, primarily stimulates peristalsis in the intestines, facilitating the movement of contents further along the...
Pyloric Obstruction01:11

Pyloric Obstruction

Pyloric obstruction, also referred to as gastric outlet obstruction, is a condition characterized by narrowing or blockage at the pylorus—the muscular valve regulating the flow of stomach contents into the duodenum. When this passage becomes impaired, the stomach cannot effectively empty its contents into the small intestine. This disruption leads to a range of gastrointestinal symptoms, including early satiety, bloating, epigastric pain, postprandial nausea, persistent vomiting, and...