AJP - Cell Physiology, Vol 254, Issue 2 C251-C257, Copyright © 1988 by American Physiological Society
Aminoglycoside-induced alterations in apical membranes of kidney epithelial cell line (LLC-PK1)
K. Inui, H. Saito, T. Iwata and R. Hori
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
Aminoglycoside-induced renal cell injury was investigated using the LLC-PK1
pig kidney epithelial cell line. The development of aminopeptidase and
gamma-glutamyltransferase, marker enzymes for apical membranes, was
inhibited in the LLC-PK1 cells cultured with gentamicin. The inhibitory
effect of gentamicin on the enzyme activities was dose dependent and was
related to its accumulation within the cells. The development of Na+
-dependent active transport of alpha-methyl-D-glucoside, a nonmetabolizable
hexose, was also inhibited by treatment with gentamicin. Inhibitions in
apical membrane enzyme activities and Na+ -dependent transport of
alpha-methyl-D-glucoside were associated with the elevation of cytosolic
free calcium, determined with a fluorescent indicator fura-2. The
correlation between the alterations in apical membrane functions and the
increase in cytosolic free calcium concentration was also supported by the
study using the calcium ionophore A23187. The present data suggest that
aminoglycoside-induced alterations in apical membranes of the LLC-PK1 cells
are related to the increase in cytosolic free calcium levels.
