Kinetic and specificity differences between rat, human and rabbit
na/glucose cotransporters (sglt1).
Hirayama, Bruce A., M. Pilar Lostao, Mariana Panayotova-Heiermann,
Donald D. F. Loo, Eric Turk, Ernest M. Wright.
Department of Physiology, UCLA School of Medicine, 10083 Le Conte
Avenue, Los Angeles, CA 90095-1751
APStracts 2:0242G, 1995.
The Na+ activation and substrate specificity of Na+/glucose
cotransporter (SGLT1) isoforms from human, rabbit and rat were
characterized using the Xenopus oocyte expression system and the two
-electrode voltage clamp method. We find that there are differences,
major and minor, in both the kinetics and substrate specificities
between these isoforms: the K0.5 for hexoses varies from 0.2 to
>40 mM, depending on the species and sugar; the Ki for
phlorizin, the classic competitive inhibitor of SGLT1, varies over
two orders of magnitude (rat Ki = 0.03 [mu]M vs. rabbit Ki = 1.4
[mu]M); and some glucoside inhibitors of the rabbit isoform, p
-nitrophenyl-glucose and [beta]-naphthyl-glucose, are transported by
the human and rat transporters. Na+ activation is more sensitive to
membrane potential in the human and rat isoforms compared to rabbit.
The rabbit isoform has a higher apparent affinities for [alpha]
-methylglucose and 3-O-methylglucose by a factor of 2 than either
human or rat. These results can be quantitatively fitted by our six
-state kinetic model of SGLT1, providing insight as to the processes
involved in these changes. For example the model predicts that Na
binding (k12) in human and rat SGLT1 are similar, but are 4-fold
larger than rabbit, whereas sugar binding (k23) in rabbit and rat are
similar, but twice the value for human. The differences in the
primary amino acid sequences between these three homologous proteins
must account for the kinetic and substrate specificity differences,
and comparisons of the functional properties and amino acid sequences
of SGLT1 isoforms provides useful information about
structure/function relationships.
Received 7 August 1995; accepted in final form 9 November 1995.
APS Manuscript Number G332-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95