CHOLECYSTOKININ--ROLE IN POSTPRANDIAL GASTRIC MOTILITY

Project: Research project

Project Details

Description

The control of gastric motility and emptying following a meal is mediated
by both hormonal and neural pathways. The aim of this proposal is to
establish a role for cholecystokinin (CCK) in mediating changes in motility
and emptying in response to duodenal stimulation, and investigate its
pathways and mechanisms of action. In particular, the role of visceral
afferent pathways in mediating changes in gastroduodenal motility induced
by CCK and duodenal stimulants will be studied. Changes in gastroduodenal motility and gastric emptying in response to
duodenal perfusion with protein, soya bean trypsin inhibitor, acid and
glucose and duodenal distension and exogenous will be determined in
anesthetized rats. Intraluminal pressure in the gastric corpus, antrum and
duodenum will be measured using a multilumen catheter for perfused side
hole manometry in combination with a sleeve sensor to simultaneously
measure pyloric pressure. Gastric emptying studies will be carried out in
conscious rats fitted with gastric fistulas using the double sampling
technique. The role of CCK will be determined using a specific receptor antagonist and
by immunoneutralization with a CCK monclonal antibody binding. The afferent
pathways by which duodenal stimulation and CCK act will be studied using
direct application of the sensory neurotoxin, capsaicin, to the vagus,
coeliac/superior mesenteric ganglion or duodenum. Local administration of
capsaicin to a peripheral nerve in adult animals produces an impairment of
afferent C-fiber function and a long-lasting insensitivity to stimulation
by physiological, electrical or chemical means. The mechanism of action of CCK will be assessed in electrophysiological
recordings of vagal afferent fibers mediating intestinal mechano- and
chemoreceptor discharge. The response of these afferents to duodenal
stimulation will be studied in the presence of CCK, CCK receptor blockade
or CCK immunoneutralization. There is abundant evidence that CCK acts in the periphery to inhibit food
intake and alter feeding behaviors. There is evidence that this may be
secondary to changes in gastrointestinal motility and transit. The
elucidation of the pathway and mechanism of action of CCK on the
gastrointestinal tract will contribute to a better understanding of
postpostprandial events and consequently eating disorders.
StatusFinished
Effective start/end date8/1/896/30/20

Funding

  • National Institutes of Health
  • National Institutes of Health: $316,184.00
  • National Institutes of Health: $228,192.00
  • National Institutes of Health: $315,327.00
  • National Institutes of Health
  • National Institutes of Health: $1.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $298,178.00
  • National Institutes of Health: $382,709.00
  • National Institutes of Health
  • National Institutes of Health: $228,901.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $242,772.00
  • National Institutes of Health: $235,699.00
  • National Institutes of Health: $304,291.00
  • National Institutes of Health: $279,781.00
  • National Institutes of Health
  • National Institutes of Health: $279,781.00
  • National Institutes of Health: $344,441.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $285,185.00
  • National Institutes of Health: $297,183.00
  • National Institutes of Health: $293,069.00

ASJC

  • Medicine(all)

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.