Involvement of apolipoprotein A-IV and cholecystokinin1 receptors in exogenous peptide YY3-36-induced stimulation of intestinal feedback

K. L. Whited, P. Tso, Helen E Raybould

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Peptide YY (PYY)3-36, released by intestinal lipid elicits functional effects that comprise the intestinal feedback response to luminal nutrients, but the pathway of action is not fully characterized. The aim of the present study was to determine the role of the apolipoprotein (apo) A-IV-cholecystokinin (CCK)1 receptor (CCK1R) pathway in exogenous PYY3-36-induced activation of the gut-brain axis and inhibition of gastric emptying and food intake. PYY3-36 (5 μg/100 g ip) significantly inhibited gastric emptying of a chow meal in wild-type but not A-IV-/- mice andCCK1R receptor blockade with devazepide (10 μg/100 g), abolished PYY3-36-induced inhibition of gastric emptying. PYY3-36-induced inhibition of food intake in both ad libitum-fed and 16-h fasted mice was unaltered in A-IV-/- mice, compared with wild-type controls, or by CCK1R receptor blockade with devazepide. PYY3-36 activated neurons in the midregion of the nucleus of the solitary tract (bregma -7.32 to -7.76 mm) in A-IV+/+ mice; this was measured by immunohistochemical localization of Fos protein. PYY 3-36-induced Fos expression was significantly reduced by 65% in A-IV+/+ mice pretreated systemically with the sensory neurotoxin capsaicin (5 mg/100 g), 78% by the CCK1R antagonist, devazepide (10 μg/100 g), and 39% by the Y2R antagonist, BIIE0246 (200 and 600 μg/100 g) and decreased by 67% in apo A-IV-/- mice, compared with A-IV +/+ controls. The data suggest a role for apo A-IV and the CCK 1Rin PYY3-36-induced activation of the vagal afferent pathway and inhibition of gastric emptying, but this is likely not the pathway mediating the effects of PYY3-36 on food intake.

Original languageEnglish (US)
Pages (from-to)4695-4703
Number of pages9
JournalEndocrinology
Volume148
Issue number10
DOIs
StatePublished - Oct 2007

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ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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