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J Gastroenterol 2004; 39:940947
DOI 10.1007/s00535-004-1425-7In vivo induction of prostasin mRNA in colonic epithelial cells by
dietary sodium depletion and aldosterone infusion in ratsKouhei Fukushima, Hiroo Naito, Yuji Funayama, Hitoshi Yonezawa, Sho Haneda, Chikashi Shibata,
and Iwao SasakiDepartment of Surgery, Tohoku University, Graduate School of Medicine, 1-1 Seiryomachi, Aoba-ku, Sendai 980-8574, JapanBackground. Parallel induction of prostasin, a novel
serine protease, together with epithelial sodium channel
(ENaC) in the colon, may be essential for physiological
response to increased circulating aldosterone. The aim
of the present study was to investigate whether aldosterone induces prostasin mRNA in parallel with enhanced
expression of ENaC in colonic epithelial cells. Methods.
Sprague-Dawley rats were maintained on a sodiumdepleted diet or subjected to continuous aldosterone
infusion up to 4 weeks. Rats were necropsied at 1, 2, or
4 weeks after the beginning of each treatment. Blood
was immediately collected and the large intestine was
removed. Plasma aldosterone and arginine-vasopressin
(AVP) levels were measured by radio-immunoassay.
Epithelial cells were isolated from the right and left
colon and RNA was extracted. Expression of prostasin
and the -, -, and -subunits of ENaC was evaluated by
quantitative RT-PCR or Northern blot analysis. In
another series of experiments, T84 cells were stimulated
with aldosterone, dexamethasone, and AVP alone or
in combination, and prostasin mRNA was measured
by quantitative RT-CPR. Results. Treatment with
sodium-depleted diet and aldosterone infusion resulted
in an increase of plasma aldosterone and induction of
prostasin mRNA in the left colon. Expression of three
subunits of ENaC also increased in the left colon. Induction of prostasin mRNA was observed when T84 cells
were stimulated with corticosteroids plus AVP in vitro.
Conclusions. Aldosterone has a pivotal role for increasing expression of prostasin in epithelial cells of the
left colon. AVP may have a synergistic effect on
aldosterone-mediated prostasin induction.Key words: prostasin, aldosterone, argininevasopressin, epithelial sodium channelReceived: October 2, 2003 / Accepted: March 5, 2004
Reprint requests to: K. FukushimaIntroductionHomeostasis of water as well as sodium balance in the
body is mainly regulated by the renin-angiotensinaldosterone system in the gastrointestinal tract. Aldosterone enhances the expression of the mRNA of two
major electrolyte transport systems, epithelial sodium
channel (ENaC) and Na[H11001]-K[H11001] ATPase subunits, and activates sodium absorption.14 ENaC is thought to represent the rate-limiting step of epithelial...