Abstracts
1998 Digestive Disease Week

#990

THE SODIUM TRANSPORT-DEPENDENT ABSORPTIVE RESPONSE OF COLONIC EPITHELIUM TO PEPTIDE YY IS DECREASED IN AQUAPORIN-4 KNOCKOUT MICE. K.S. Wang, T. Ma, A.R. Komar, I Cross, A.S. Verkman, J. A. Bastidas. Department of Surgery, Stanford Univ. Sch of Med., Stanford, CA; CVRI, UCSF, San Francisco, CA.

Background: A family of water channel genes called aquaporin (AQP) are expressed in several water transporting tissues such as kidney, choroid plexus, and colon. We have recently shown that transepithelial water movement in the colon occurs in part via AQP4.

Methods: To determine if AQP4 facilitates physiologic water absorption in the colon, anesthetized 25-45 g wildtype (WT, n=6) and AQP4 knockout mice (KO, n=9) underwent jugular vein catheterization and in situ perfusion of colon (4.2-5 cm length). Colons were perfused at 3 mL/h with buffered electrolyte solution (288 mOsm) containing 14C-polyethylene glycol as a nonabsorbable volume marker. Collected effluent was analyzed for 14C radioactivity for calculation of net water flux across the colonic epithelium. After a 40 min basal period, peptide YY (PYY), a proabsorptive GI hormone, was infused intravenously (100 pmol/kg/hr) for 80 min. To determine the dependence of the PYY absorptive response on lumenal Na+, additional WT mice (n=7) were perfused with solutions (325 mOsm) containing either Na+ or choline.

Results: Basal water absorption was similar for WT (71 ± 8 µL/min/g dry colon) and KO mice (62 ± 11 µL/min/g). However, at 40 min after initiation of PYY infusion, the increase in net water absorption was significantly greater in the WT mice (70 ± 6 µL/min/g) than in KO mice (36 ± 10 µL/min/g, p<0.05). At 80 min, the increases in net water absorption were 77 ± 12 µL/min/g in WT mice and 57 ± 14 µL/min/g in KO mice. The increase in net water absorption in WT mice in response to PYY was significantly greater in the presence of Na+ (145 ± 3 µL/min/g) than in the presence of choline (49 ± 5 µL/min/g, p<0.05).

Conclusion: These data suggest that the absorptive response to PYY in the colon is a Na+ transport dependent phenomenon and that transepithelial PYY stimulated water absorption is facilitated by AQP4.

Copyright 1996 - 1998, SSAT, Inc. Revised 29 June 1998.