Short-chain fatty acids inhibit camp-mediated chloride secretion in
rat colon.
Dagher, Pierre C., Richard W. Egnor, Angelagrace Taglietta
-Kohlbrecher, and Alan N. Charney.
Nephrology Section, VA Medical Center, New York, NY, New York
University School of Medicine, New York, NY 10010
APStracts 3:0221C, 1996.
Butyrate stimulates salt absorption in mammalian colon. We examined if
butyrate also affects Cl- secretion. Mucosal segments of distal colon
of male Sprague-Dawley rats and T84 cells were studied in Ussing
chambers. In control tissues, 1 mM dibutyryl cyclic AMP (dbcAMP)
increased short circuit current (Isc) and serosal to mucosal Cl- flux
(J) by 3.2 +/- 0.8 and 2.9 +/- 0.8 [mu]eq.cm-2.h-1, respectively.
Mucosal or serosal 25 mM butyrate prevented dbcAMP-induced increases
in Isc and J. Four and 8 mM butyrate caused half-maximal inhibition
of the increases in J and Isc respectively. Butyrate also inhibited
basal J (by 2.0 +/- 0.4 [mu]eq.cm-2.h-1), but not carbachol-mediated
Cl- secretion. The relative inhibitory potency at 25 mM of other
short-chain fatty acids (SCFAs) paralleled their degree of cellular
metabolism: butyrate > acetate = propionate > isobutyrate.
At 25 mM, all SCFAs reduced mucosal pHi transiently by 0.1 pH unit.
In intact T84 cells, 50 mM butyrate inhibited the dbcAMP-induced rise
in Isc by 55%. In T84 cells with nystatin-permeabilized basolateral
membranes, butyrate inhibited the increase in Isc by 82%. We conclude
that butyrate inhibits basal and cAMP-mediated Cl- secretion by a
mechanism independent of pHi and possibly located at the apical
membrane.
Received 16 January 1996; accepted in final form 7 June 1996.
APS Manuscript Number C24-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996