Effect of 2-chloropropionate on initial lactate uptake by rat
skeletal muscle sarcolemmal vesicles.
Granier, P., H. Dubouchaud, N. Eydoux, J. Mercier, Ch. Pr[acute]efaut.
Laboratoire de Physiologie des Interactions, Service d'Exploration
de la Fonction Respiratoire, H[circumflex]opital A. de Villeneuve,
371, Avenue du Doyen G. Giraud, 34295 MONTPELLIER cedex 5, FRANCE
APStracts 3:0354A, 1996.
2-chloropropionate (2-CP) is a halogenated monocarboxylic acid
generally used to decrease blood lactate concentration in various
metabolic states. To investigate whether it has an inhibitory effect
on sarcolemmal lactate transport, we compared the initial rate of
lactate transport in sarcolemmal membrane vesicles purified from 20
male Wistar rats, with 2-CP and without. Transport by these vesicles
was measured as uptake of [U-14C] L(+)-lactate under pH gradient
-stimulated cis-inhibition. The time courses of 1 mM L-(+)-lactate
uptake into vesicles both with and without 10 mM 2-CP (L- or D-)
displayed saturation kinetics. Lactate uptake values were lower with
10 mM L-2CP and 10 mM D-2CP in comparison to the control values. 10
mM L-2CP and 10 mM D-2CP significantly inhibited 1 mM L-(+)-lactate
uptake (55.7 % +/- 9.1 % and 53.5 % +/- 12.1 % ; p < 0.001),
whereas a smaller inhibition was observed with a higher lactate
concentration of 50 mM (40.2 % +/- 11.2 % and 38.6 % +/- 12.4 % ; p
< 0.001 and p < 0.05). However, a higher D-2CP
concentration (50 mM) increased the inhibition of pH-stimulated 1 mM
L-(+)-lactate uptake (77.0 % +/- 9.4 % ; p < 0.001). D-2CP had a
trans-stimulation effect on the initial rate of lactate efflux of 1
mM L(+)-lactate compared to baseline efflux (9.5 0.8 vs 5.1 0.4
nmol.min-1..mg-1protein, p < 0.05). 2-CP significantly inhibited
the initial rate of lactate uptake in skeletal muscle sarcolemmal
membrane vesicles. This result suggests that 2-CP is a non
-stereoselective substrate of the lactate muscle carrier that impairs
lactate transport.
Received 18 July 1995; accepted in final form 11 July 1996.
APS Manuscript Number A782-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 August 1996