TY - JOUR
T1 - Targeted disruption of the murine CCK1 receptor gene reduces intestinal lipid-induced feedback inhibition of gastric function
AU - Whited, K. L.
AU - Thao, D.
AU - Lloyd, Kevin C K
AU - Kopin, A. S.
AU - Raybould, Helen E
PY - 2006
Y1 - 2006
N2 - Cholecystokinin (CCK), acting at CCK1 receptors (CCK 1Rs) on intestinal vagal afferent terminals, has been implicated in the control of gastrointestinal function and food intake. Using CCK 1R-/- mice, we tested the hypothesis that lipid-induced activation of the vagal afferent pathway and intestinal feedback of gastric function is CCK1R dependent. In anesthetized CCK1R +/+ ("wild type") mice, meal-stimulated gastric acid secretion was inhibited by intestinal lipid infusion; this was abolished in CCK1R-/- mice. Gastric emptying of whole egg, measured by nuclear scintigraphy in awake mice, was significantly faster in CCK 1R-/- than CCK1R+/+ mice. Gastric emptying of chow was significantly slowed in response to administration of CCK-8 (22 pmol) in CCK1R+/+ but not CCK1R -/- mice. Activation of the vagal afferent pathway was measured by immunohistochemical localization of Fos protein in the nucleus of the solitary tract (NTS; a region where vagal afferents terminate). CCK-8 (22 pmol ip) increased neuronal Fos expression in the NTS of fasted CCK1R +/+ mice; CCK-induced Fos expression was reduced by 97% in CCK 1R-/- compared with CCK1R+/+ mice. Intralipid (0.2 ml of 20% Intralipid and 0.04 g lipid), but not saline, gavage increased Fos expression in the NTS of fasted CCK1R+/+ mice; lipid-induced Fos expression was decreased by 47% in CCK1R -/- compared with CCK1R+/+ mice. We conclude that intestinal lipid activates the vagal afferent pathway, decreases gastric acid secretion, and delays gastric emptying via a CCK1R-dependent mechanism. Thus, despite a relatively normal phenotype, intestinal feedback in response to lipid is severely impaired in these mice.
AB - Cholecystokinin (CCK), acting at CCK1 receptors (CCK 1Rs) on intestinal vagal afferent terminals, has been implicated in the control of gastrointestinal function and food intake. Using CCK 1R-/- mice, we tested the hypothesis that lipid-induced activation of the vagal afferent pathway and intestinal feedback of gastric function is CCK1R dependent. In anesthetized CCK1R +/+ ("wild type") mice, meal-stimulated gastric acid secretion was inhibited by intestinal lipid infusion; this was abolished in CCK1R-/- mice. Gastric emptying of whole egg, measured by nuclear scintigraphy in awake mice, was significantly faster in CCK 1R-/- than CCK1R+/+ mice. Gastric emptying of chow was significantly slowed in response to administration of CCK-8 (22 pmol) in CCK1R+/+ but not CCK1R -/- mice. Activation of the vagal afferent pathway was measured by immunohistochemical localization of Fos protein in the nucleus of the solitary tract (NTS; a region where vagal afferents terminate). CCK-8 (22 pmol ip) increased neuronal Fos expression in the NTS of fasted CCK1R +/+ mice; CCK-induced Fos expression was reduced by 97% in CCK 1R-/- compared with CCK1R+/+ mice. Intralipid (0.2 ml of 20% Intralipid and 0.04 g lipid), but not saline, gavage increased Fos expression in the NTS of fasted CCK1R+/+ mice; lipid-induced Fos expression was decreased by 47% in CCK1R -/- compared with CCK1R+/+ mice. We conclude that intestinal lipid activates the vagal afferent pathway, decreases gastric acid secretion, and delays gastric emptying via a CCK1R-dependent mechanism. Thus, despite a relatively normal phenotype, intestinal feedback in response to lipid is severely impaired in these mice.
KW - Cholecystokinin
KW - Gastric acid secretion
KW - Gastric emptying
KW - Nucleus of the solitary tract
KW - Vagal afferent
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U2 - 10.1152/ajpgi.00569.2005
DO - 10.1152/ajpgi.00569.2005
M3 - Article
C2 - 16574983
AN - SCOPUS:33745764827
VL - 291
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
SN - 1931-857X
IS - 1
ER -