Colon water transport in transgenic mice lacking aquaporin-4 water channels.
Transgenic null mice were used to test the hypothesis that water channel aquaporin-4 (AQP4) is involved in colon water transport and fecal dehydration. AQP4 was immunolocalized to the basolateral membrane of colonic surface epithelium of wild-type (+/+) mice and was absent in AQP4 null (-/-) mice. The transepithelial osmotic water permeability coefficient (P(f)) of in vivo perfused colon of +/+ mice, measured using the volume marker (14)C-labeled polyethylene glycol, was 0.016 +/- 0.002 cm/s. P(f) of proximal colon was greater than that of distal colon (0.020 +/- 0.004 vs. 0. 009 +/- 0.003 cm/s, P < 0.01). P(f) was significantly lower in -/- mice when measured in full-length colon (0.009 +/- 0.002 cm/s, P < 0. 05) and proximal colon (0.013 +/- 0.002 cm/s, P < 0.05) but not in distal colon. There was no difference in water content of cecal stool from +/+ vs. -/- mice (0.80 +/- 0.01 vs. 0.81 +/- 0.01), but there was a slightly higher water content in defecated stool from -/- mice (0.68 +/- 0.01 vs. 0.65 +/- 0.01, P < 0.05). Despite the differences in water permeability with AQP4 deletion, theophylline-induced secretion was not impaired (50 +/- 9 vs. 51 +/- 8 microl. min(-1). g(-1)). These results provide evidence that transcellular water transport through AQP4 water channels in colonic epithelium facilitates transepithelial osmotic water permeability but has little or no effect on colonic fluid secretion or fecal dehydration.
Department of Surgery, Stanford University School of Medicine, CA 94143-0521, USA.
K S
KS
Wang
T
T
Ma
F
F
Filiz
A S
AS
Verkman
J A
JA
Bastidas
D000818:Animals; D051400:Aquaporin 3; D051401:Aquaporin 4; D020346:Aquaporins / Q000032:analysis / Q000235:genetics*; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D003106:Colon / Q000737:chemistry / Q000378:metabolism*; D005243:Feces / Q000737:chemistry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000502:physiology; D007413:Intestinal Mucosa / Q000737:chemistry / Q000378:metabolism; D007473:Ion Channels; D051379:Mice; D018345:Mice, Knockout; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology; D014158:Transcription, Genetic / Q000502:physiology; D014867:Water / Q000032:analysis / Q000378:metabolism*; D014882:Water-Electrolyte Balance / Q000502:physiology
C496028:Aqp3 protein, mouse; C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D020346:Aquaporins; D002250:Carbon Radioisotopes; D007473:Ion Channels; D010726:Phosphodiesterase Inhibitors; C108330:aquaporin 8; D014867:Water; D051400:Aquaporin 3; D013806:Theophylline