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1 Conservatoire National des
Arts et Métiers,
Stimulating water
absorption in the colon represents an important target to reduce stool
output in secretory diarrhea. Recently, a 153-amino-acid peptide was
isolated from porcine upper small intestine and purified, taking into
account the increase of water absorption in guinea pig gallbladder.
Accordingly, this peptide was named sorbin. The aim of the present
study was to determine if the COOH-terminal heptapeptide of sorbin
(C7-sorbin) participates in the
regulation of electrolyte transport in the colon. Different regions
(from duodenum to colon) of stripped intestinal mucosa from rats or
humans were mounted in Ussing chambers to measure the changes in
short-circuit current
(
Isc) and
net 22Na and
36Cl fluxes
(JNanet and
JClnet) after serosal exposure
of 10
7 to
10
3 M
C7-sorbin. In fasted rat
intestine, C7-sorbin
(10
4 M) induced an
immediate reduction in
Isc in the distal
ileum and proximal and distal colon but not in the duodenum and
jejunum. In the colon,
Isc reduction and
JNanet and JClnet stimulation were dose
dependent (EC50 = 2 × 10
5 M). At
10
3 M, maximal effect was
observed (
Isc =
1.14 ± 0.05,
JNanet = +4.97 ± 1.38, and
JClnet = +9.25 ± 1.44 µeq · h
1 · cm
2).
C7-sorbin
(10
3 M) inhibited the
increase in Isc
induced by a series of 10 secretory agents such as secretin, vasoactive
intestinal peptide, PGE2, and
serotonin. In HT-29-Cl19A cells,
C7-sorbin induced an increase in
Isc, with a
maximal effect at 10
3 M
(
Isc = 0.29 ± 0.10 µeq · h
1 · cm
2).
In human intestine, a dose-dependent decrease in
Isc was observed in right and sigmoid colons in basal and stimulated conditions (EC50
10
5 M; at
10
4 M,
Isc =
2.66 ± 0.17 µeq · h
1 · cm
2)
but not in the jejunum. The results indicate that
C7-sorbin stimulated NaCl neutral
absorption and inhibited electrogenic Cl
in rat and human
intestinal epithelia. In addition, the antisecretory effect was
essentially observed in the distal part of both rat and human intestine
and the magnitude of the proabsorptive effect was directly related to
the magnitude of the previously induced secretion.
sodium chloride absorption; ion transport; colon
This article has been cited by other articles:
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F A. El Fadil-Nicol, F Berger, M Descroix-Vagne, and D Pansu Presence of sorbin in human digestive tract and endocrine digestive tumours Gut, February 1, 2000; 46(2): 182 - 190. [Abstract] [Full Text] [PDF] |
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