Targeted disruption of the murine CCK<sub>1</sub> receptor gene reduces intestinal lipid-induced feedback inhibition of gastric function

Whited, K. L.; Thao, D. T. P.; Lloyd, Kevin C K; Kopin, Alan S.; Raybould, Helen E.

doi:10.1152/ajpgi.00569.2005

Cited by 55 publications

(43 citation statements)

References 35 publications

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“…It may also be that since central influences play a larger role in upper GI motility, particularly gastric emptying, the effects of enteric dopamine damage are less pronounced. It is less likely that our methods for detection of upper GI behavioral abnormalities are insufficiently sensitive to detect a small change (Travagli, et al, 2006, Whited, et al, 2006. Finally, although unlikely, there is the possibility that enteric neurons in the lower GI tract are more sensitive to MPTP toxicity.…”

Section: Discussionmentioning

confidence: 96%

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Loss of enteric dopaminergic neurons and associated changes in colon motility in an MPTP mouse model of Parkinson's disease

Anderson

Noorian

Taylor

et al. 2007

Experimental Neurology

207

196

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Gastrointestinal (GI) dysfunction is the most common non-motor symptom of Parkinson's disease (PD). Symptoms of GI dysmotility include early satiety and nausea from delayed gastric emptying, bloating from poor small bowel coordination, and constipation and defecatory dysfunction from impaired colonic transit. Understanding the pathophysiology and treatment of these symptoms in PD patients has been hampered by the lack of investigation into GI symptoms and pathology in PD animal models. We report that the prototypical parkinsonian neurotoxin, MPTP (1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine), is a selective dopamine neuron toxin in the enteric nervous system (ENS). When examined 10 days after treatment, there was a 40% reduction of dopamine neurons in the ENS of C57Bl/6 mice administered MPTP (60 mg/kg). There were no differences in the density of cholinergic or nitric oxide neurons. Electrophysiological recording of neural-mediated muscle contraction in isolated colon from MPTP-treated animals confirmed a relaxation defect associated with dopaminergic degeneration. Behaviorally, MPTP induced a transient increase in colon motility, but no changes in gastric emptying or small intestine transit. These results provide the first comprehensive assessment of gastrointestinal pathophysiology in an animal model of PD. They provide insight into the impact of dopaminergic dysfunction on gastrointestinal motility and a benchmark for assessment of other PD model systems.

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Section: Discussionmentioning

confidence: 96%

“…Two hours later, animals were killed and the stomach contents were weighed. Food was weighed before and after the feeding period to determine the amount consumed (Whited, et al, 2006).…”

Section: Solid Gastric Emptyingmentioning

confidence: 99%

Loss of enteric dopaminergic neurons and associated changes in colon motility in an MPTP mouse model of Parkinson's disease

Anderson

Noorian

Taylor

et al. 2007

Experimental Neurology

207

196

View full text Add to dashboard Cite

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“…Similarly, the literature demonstrates the power of small animal scintigraphy to document biological effects in knockouts as well as pharmacological modulation (137,138).…”

Section: Gastric Emptying Scintigraphymentioning

confidence: 95%

Methods for measurement of gastric motility

Szarka¹,

Camilleri²

2009

American Journal of Physiology-Gastrointestinal and Liver Physi

104

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Szarka LA, Camilleri M. Methods for measurement of gastric motility. Am J Physiol Gastrointest Liver Physiol 296: G461-G475, 2009. First published January 15, 2009 doi:10.1152/ajpgi.90467.2008There is an array of tests available to measure gastric motility. Some tests measure end points, such as gastric emptying, that result from several different functions, whereas other tests are more specific and test only a single parameter, such as contractility. This article reviews the tests most commonly available in practice and research to evaluate in vivo the gastric functions of emptying, accommodation, contractility, and myoelectrical activity. The rationale for testing, the relative strengths and weaknesses of each test, and technical details are summarized. We also briefly indicate the applications and validations of the tests for use in experimental animal studies. contractility; emptying; accommodation; gastroparesis; dyspepsia ASSESSMENT OF THE MOTOR FUNCTIONS (motility) of the stomach is important in studies of gastric physiology and pathophysiology. Although not generally applied in gastroenterological practice, there is increasing use of tests to evaluate gastric function, particularly less invasive tests in clinical settings.There is an array of tests available to measure gastric motility. Some tests measure end points, such as gastric emptying, that result from several different functions, whereas other tests are more specific and test only a single parameter, such as contractility. This article reviews the tests most commonly available in practice and research to evaluate in vivo the gastric functions of emptying, accommodation, contractility, and myoelectrical activity. The rationale for testing, the relative strengths and weaknesses of each test, and technical details are summarized. A brief discussion is also provided for methods that have been used in animals to study motor functions of the stomach in animals. Tests to Evaluate Gastric Emptying of SolidsGastric emptying is a composite end point reflecting a variety of functions including gastric accommodation, the pressure gradient between the proximal and distal stomach, and antropyloroduodenal contractility and coordination. The trituration of solids and emptying of solid and liquid food from the stomach are arguably the most important physiological functions of the stomach. Abnormal gastric emptying, either accelerated at 1 h or delayed at 4 h, is among the factors that contribute to reporting of dyspepsia or the development of postprandial symptoms after meal challenge (35). For all tests of gastric motility and emptying, there are standard precautions (1): 1) Drugs affecting gastric motility (e.g., anticholinergics, narcotics, and prokinetics) are stopped for 48 h prior to the test, and the study is performed in the morning after an overnight fast. 2) Diabetic subjects should have a glucose level Ͻ275 mg/dl. 3) At the time the meal is ingested, Type 1 diabetic patients should receive half of their normal insulin dose. Gastric Emptying Scintigrap...

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“…Little is known about how feeding behavior of CCK 1 R -/-mice is altered by diet composition. The CCK 1 R is involved in the detection of dietary lipid within the intestine in mice [17], but it is not clear whether these mice are able to respond to the satiating effects of lipid in the diet. We hypothesized that the CCK 1 R is involved in meal termination, particularly in the presence of high lipid content of the ingested diet.…”

Section: Introductionmentioning

confidence: 99%

CCK1 receptor is essential for normal meal patterning in mice fed high fat diet

Donovan

Paulino

Raybould

2007

Physiology & Behavior

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Cholecystokinin (CCK), released by lipid in the intestine, initiates satiety by acting at cholecystokinin type 1 receptors (CCK 1 Rs) located on vagal afferent nerve terminals located in the wall of the gastrointestinal tract. In the present study, we determined the role of the CCK 1 R in the short term effects of a high fat diet on daily food intake and meal patterns using mice in which the CCK 1 R gene is deleted. CCK 1 R -/-and CCK 1 R +/+ mice were fed isocaloric high fat (HF) or low fat (LF) diets ad libitum for 18 hours each day and meal size, meal frequency, intermeal interval, and meal duration were determined. Daily food intake was unaltered by diet in the CCK 1 R -/-compared to CCK 1 R +/+ mice. However, meal size was larger in the CCK 1 R -/-mice compared to CCK 1 R +/+ mice when fed a HF diet, with a concomitant decrease in meal frequency. Meal duration was increased in mice fed HF diet regardless of phenotype. In addition, CCK 1 R -/-mice fed a HF diet had a 75% decrease in the time to 1 st meal compared to CCK 1 R +/+ mice following a 6 hr fast. These data suggest that lack of the CCK 1 R results in diminished satiation, causing altered meal patterns including larger, less frequent meals when fed a high fat diet. These results suggest that the CCK 1 R is involved in regulating caloric intake on a meal to meal basis, but that other factors are responsible for regulation of daily food intake.

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Targeted disruption of the murine CCK₁ receptor gene reduces intestinal lipid-induced feedback inhibition of gastric function

Abstract: Targeted disruption of the murine CCK 1 receptor gene reduces intestinal lipid-induced feedback inhibition of gastric function.

Cited by 55 publications

References 35 publications

Loss of enteric dopaminergic neurons and associated changes in colon motility in an MPTP mouse model of Parkinson's disease

Loss of enteric dopaminergic neurons and associated changes in colon motility in an MPTP mouse model of Parkinson's disease

Methods for measurement of gastric motility

CCK1 receptor is essential for normal meal patterning in mice fed high fat diet

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Targeted disruption of the murine CCK1 receptor gene reduces intestinal lipid-induced feedback inhibition of gastric function

Abstract: Targeted disruption of the murine CCK 1 receptor gene reduces intestinal lipid-induced feedback inhibition of gastric function.

Cited by 55 publications

References 35 publications

Loss of enteric dopaminergic neurons and associated changes in colon motility in an MPTP mouse model of Parkinson's disease

Loss of enteric dopaminergic neurons and associated changes in colon motility in an MPTP mouse model of Parkinson's disease

Methods for measurement of gastric motility

CCK1 receptor is essential for normal meal patterning in mice fed high fat diet

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Targeted disruption of the murine CCK₁ receptor gene reduces intestinal lipid-induced feedback inhibition of gastric function