Inhibition of aquaporin-3 water channel in the colon induces diarrhea.
Aquaporin (AQP) 3, which is predominantly expressed in the colon, is considered to play an important role in regulating the fecal water content in the colon. In this study, the role of AQP3 in the colon was examined using HgCl(2) and CuSO(4), which are known to inhibit AQP3 function. The fecal water content was measured up to 1 h after the rectal administration of HgCl(2) or CuSO(4) to rats. The results showed that the fecal water content in the HgCl(2) administration group increased significantly to approximately 4 times that in the control group, and severe diarrhea was observed. However, no changes were observed in the mRNA expression level of the osmoregulatory genes (sodium myo-inositol transporter and taurine transporter) and the level and distribution of AQP3 protein expression, as determined 1 h after the administration of HgCl(2). Comparable results were observed in the CuSO(4) administration group. The results of this study indicated that the inhibition of AQP3 function in the colon caused diarrhea. Therefore, it has been revealed that the fecal water content in the colon is controlled by the transport of water from the luminal side to the vascular side, which is mediated by AQP3. Our findings suggest that a drug that modulates the function or expression of AQP3 in the colon may represent a new target for the development of laxatives.
Department of Clinical Pharmacokinetics, Hoshi University, Shinagawa-ku, Tokyo, Japan.
Nobutomo
N
Ikarashi
Risako
R
Kon
Tomohiko
T
Iizasa
Noriko
N
Suzuki
Reiko
R
Hiruma
Kiyomi
K
Suenaga
Takahiro
T
Toda
Makoto
M
Ishii
Motohiro
M
Hoshino
Wataru
W
Ochiai
Kiyoshi
K
Sugiyama
D000818:Animals; D051400:Aquaporin 3 / Q000037:antagonists & inhibitors / Q000502:physiology*; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D019327:Copper Sulfate / Q000494:pharmacology; D003967:Diarrhea / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D005243:Feces / Q000737:chemistry*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics; D008627:Mercuric Chloride / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D027981:Symporters / Q000235:genetics; D014867:Water / Q000378:metabolism*; D000099247:Taurine Transporters
D051400:Aquaporin 3; D019327:Copper Sulfate; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008627:Mercuric Chloride; D012333:RNA, Messenger; D027981:Symporters; D014867:Water; D000099247:Taurine Transporters; C496029:Aqp3 protein, rat; C571821:sodium-myo-inositol cotransporter, rat