AJP - Cell Physiology, Vol 261, Issue 3 C506-C514, Copyright © 1991 by American Physiological Society
Cis-inhibition and trans-stimulation of cationic amino acid transport in the perfused rat pancreas
J. H. Sweiry, M. Munoz and G. E. Mann
Biomedical Sciences Division, King's College London, United Kingdom.
Transport of cationic amino acids in the isolated perfused rat pancreas was
studied using dual-isotope dilution techniques. At 50 microM substrate
concentration, unidirectional tracer uptakes for L-arginine (56 +/- 1%),
L-lysine (49 +/- 2%), and L-ornithine (44 +/- 3%) were followed by rapid
tracer efflux. In the presence of Na+, influx of L-arginine [Michaelis
constant (Km) = 1.74 +/- 0.15 mM, maximum velocity (Vmax) = 1.97 +/- 0.07
mumol.min-1.g-1] and L-lysine (Km = 2.48 +/- 0.17 mM, Vmax = 2.42 +/- 0.08
mumol.min-1.g-1) was mediated by a common transport system, sensitive to
cis-inhibition by L-ornithine, 2,4-L-diaminobutyric acid, D-lysine, and
D-arginine. Substrates for system A [alpha-(methylamino)isobutyric acid]
and an anionic carrier (L-aspartate) were poor cis-inhibitors of L-arginine
entry. Removal of Na+ resulted in a 40% reduction in cationic amino acid
influx. After cell loading (20 min), L-[3H]-lysine cleared predominantly
from a slowly exchanging pool with a rate constant of 5.97 +/- 0.67 min. An
influx/efflux permeability ratio of 14.5 +/- 1.6 was determined, and efflux
of L-lysine was trans-stimulated by vascular challenges with cationic or
large neutral amino acids. The specificity, relative Na+ independence, and
exchange properties of this saturable cationic amino acid transporter in
the pancreatic epithelium resemble those reported for system y+ in cultured
fibroblasts and hepatocytes.
