title: Cholecystokinin mediation of colonic absorption via peptide YY: foregut-hindgut axis.
abstract: Peptide YY (PYY), a 36-amino-acid polypeptide, is found in abundance in the colon, a region where its physiologic roles are unknown. Previous studies have revealed a substantial increase in plasma PYY after cholecystokinin (CCK) administration. PYY is released from the hindgut in response to a meal and inhibits CCK release. In this study we evaluated the effects of CCK and PYY on intestinal absorption of water and electrolytes. Colonic, ileal, or jejunal Thiry-Vella fistulas (TVFs) were created in 12 dogs, and intestinal continuity was reestablished. The TVFs were perfused with an isotonic buffer solution containing [14C] PEG as a volume marker. Electrolyte and water transport were measured every 15 minutes, and plasma PYY and CCK levels were measured by radioimmunoassay. Group 1 dogs received an intravenous bolus of MK329, a specific CCK receptor antagonist, at 20 nmol/kg after a standard mixed meal; group 2 colonic TVF dogs received a meal and an intravenous bolus of PYY polyclonal antibody at 1 mg/kg. Postprandially, all three regions of the bowel became significantly proabsorptive for water, sodium, and chloride. In the colon postprandial absorption was abolished by MK329 starting 60 minutes after a meal, whereas specific CCK receptor blockade blunted ileal absorption. CCK receptor blockade did not affect postprandial absorption in the jejunum. Postprandial PYY levels did not rise in MK329-treated animals. PYY antibody reduced colonic absorption during the postprandial phase. Reduction of meal-induced colonic absorption and PYY release by MK329 in awake dogs suggests an important foregut-hindgut hormonal feedback loop. Foregut-derived CCK stimulates hindgut PYY release, which in turn stimulates colonic absorption while inhibiting further CCK release.
authors.affiliation: Department of Surgery, UCLA Center for Health Sciences and Sepulveda VA Medical Center, 72-215 CHS, 10833 LeConte Avenue, Los Angeles, California 90024, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Liu
authors.forename: O J
authors.initials: OJ
authors.lastname: Hines
authors.forename: T R
authors.initials: TR
authors.lastname: Newton
authors.forename: T E
authors.initials: TE
authors.lastname: Adrian
authors.forename: M J
authors.initials: MJ
authors.lastname: Zinner
authors.forename: S W
authors.initials: SW
authors.lastname: Ashley
authors.forename: D W
authors.initials: DW
authors.lastname: McFadden
mesh_terms: D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002021:Buffers; D002250:Carbon Radioisotopes; D002712:Chlorides / Q000493:pharmacokinetics; D002766:Cholecystokinin / Q000032:analysis / Q000097:blood / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D020109:Devazepide; D004063:Digestion; D004285:Dogs; D004573:Electrolytes / Q000493:pharmacokinetics; D005246:Feedback / Q000187:drug effects; D005260:Female; D005768:Gastrointestinal Hormones / Q000097:blood / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects*; D007552:Isotonic Solutions; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D019894:Peptide YY; D010455:Peptides / Q000097:blood / Q000494:pharmacology*; D011949:Receptors, Cholecystokinin / Q000032:analysis; D012964:Sodium / Q000493:pharmacokinetics; D014867:Water / Q000378:metabolism
chemical_list: D001570:Benzodiazepinones; D002021:Buffers; D002250:Carbon Radioisotopes; D002712:Chlorides; D004573:Electrolytes; D005768:Gastrointestinal Hormones; D006727:Hormone Antagonists; D007552:Isotonic Solutions; D010455:Peptides; D011949:Receptors, Cholecystokinin; D014867:Water; D019894:Peptide YY; D002766:Cholecystokinin; D012964:Sodium; D020109:Devazepide