Gentamicin-induced decreases in glomerular filtration rate have been associ
ated to a marked decline in the glomerular capillary ultrafiltration coeffi
cient which could be due to an active contraction of mesangial cells. In th
e present work we assessed a possible role of cytosolic Ca2+ as a mediator
that leads to contraction and proliferation induced by gentamicin on mesang
ial cells. Gentamicin (10(-5)M) induced an increase in cytosolic free Ca2+,
that was fully inhibited by the calcium channel blocker, verapamil, and by
the endoplasmic reticulum calcium release blocker, TMB-8. Gentamicin induc
ed a planar surface area reduction in cultured mesangial cells, that was bl
unted by verapamil and TMB-8. Gentamicin also stimulated [H-3]thymidine inc
orporation into DNA and increased viable cell number, effects that were red
uced by both, verapamil and TMB-8. Gentamicin stimulated the expression of
the AP1 protein; this expression was partially blunted by verapamil and TMB
-8. Moreover, verapamil inhibited gentamicin-induced PAF synthesis from mes
angial cells. in summary, gentamicin directly raised intracellular Ca2+ act
ivating both calcium influx from external medium and calcium release from i
nternal stores. This increase is responsible of cellular activation (contra
ction and proliferation) and PAF synthesis induced by gentamicin on mesangi
al cells. Copyright (C) 2000 S. Karger AG, Basel.