CHOLECYSTOKININ MEDIATION OF COLONIC ABSORPTION VIA PEPTIDE YY - FOREGUT-HINDGUT AXIS

Peptide YY (PYY), a 36-amino-acid polypeptide, is found in abundance i n the colon, a region where its physiologic roles are unknown. Previou s studies have revealed a substantial increase in plasma PYY after cho lecystokinin (CCK) administration. PYY is released from the hindgut in response to a meal and inhibits CCK release. In this study we evaluat ed the effects of CCK! and PW on intestinal absorption of water and el ectrolytes. Colonic, ileal, or jejunal Thiry-Vella fistulas (TVFs) wer e created in 12 dogs, and intestinal continuity was reestablished. The TVFs were perfused with an isotonic buffer solution containing [C-14] PEG as a volume marker. Electrolyte and water transport were measured every 15 minutes, and plasma PW and CCK levels were measured by radio immunoassay. Group 1 dogs received an intravenous bolus of MK329, a sp ecific CCK receptor antagonist, at 20 nmol/kg after a standard mixed m eal; group 2 colonic TVF dogs received a meal and an intravenous bolus of PYY polyclonal antibody at 1 mg/kg. Postprandially, all three regi ons of the bower became significantly proabsorptive for water, sodium, and chloride. In the colon postprandial absorption was abolished by M K329 starting 60 minutes after a meal, whereas specific CCK receptor b lockade blunted ileal absorption. CCK receptor blockade did not affect postprandial absorption in the jejunum. Postprandial PYY levels did n ot rise in MK329-treated animals. PW antibody reduced colonic absorpti on during the postprandial phase. Reduction of meal-induced colonic ab sorption and PW release by MK329 in awake dogs suggests an important f oregut-hindgut hormonal feedback loop. Foregut-derived CCK stimulates hindgut PYY release, which in turn stimulates colonic absorption while inhibiting further CCK release.