Vm. Rajendran et Hj. Binder, APICAL MEMBRANE CL-BUTYRATE EXCHANGE - MECHANISM OF SHORT-CHAIN FATTY-ACID STIMULATION OF ACTIVE CHLORIDE ABSORPTION IN RAT DISTAL COLON, The Journal of membrane biology, 141(1), 1994, pp. 51-58
The cellular model of short chain fatty acid stimulation of electroneu
tral Na-Cl absorption in large intestine proposes that SCFA, following
its uptake across the apical membrane, recycles and is coupled to fun
ctional Na-H and Cl-short chain fatty acid exchanges. To establish the
presence of a Cl-butyrate exchange (used as a model short chain fatty
acid), studies of Cl-36 and C-14-butyrate uptake across apical membra
ne vesicles of rat distal colon were performed. An outward butyrate-gr
adient stimulated transient accumulation of Cl-36 uptake that was not
inhibited by pH clamping with valinomycin (a K ionophore) and FCCP (a
proton ionophore). Outward butyrate-gradient-stimulated Cl-36 uptake w
as inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DI
DS) with a half-maximal inhibitory concentration (IC50) of 68.4 mu M,
and was saturated by both increasing extravesicular Cl concentration (
K-m for Cl of 26.8 +/- 3.4 mM and a V-max of 12.4 +/- 0.6 nmol/mg prot
ein . 9 sec) and increasing intravesicular butyrate concentration (K-m
for butyrate of 5.9 mM and a V-max for Cl of 5.9 nmol/mg protein . 9
sec). Cl-36 uptake was also stimulated by outward gradients of other s
hort chain fatty acids (e.g., propionate, acetate and formate). In con
trast, an outward Cl gradient failed to enhance C-14-butyrate uptake.
Extravesicular Cl more than extravesicular butyrate enhanced Cl-36 eff
lux from apical membrane vesicles. These studies provide compelling ev
idence for the presence of an electroneutral, pH-activated, Cl-butyrat
e exchange which in concert with Na-H exchange is the mechanism by whi
ch butyrate stimulates electroneutral Na-Cl absorption.