Gentamicin activates rat mesangial cells. A role for platelet activating factor

Abstract

Gentamicin-induced decreases in glomerular filtration rate have been associated with a marked decline in the glomerular capillary ultrafiltration coefficient which could be mediated by mesangial cell contraction or release of vasoactive hormones. We studied the effect of gentamicin on mesangial cells proliferation, contraction and Ca2+ mobilization. Moreover, we attempted to assess a possible role of platelet activating factor (PAF) as a mediator of the observed effects of gentamicin on mesangial cells. Gentamicin induced a reduction of planar surface area of cultured rat mesangial cells that was blunted by the PAF-antagonist, BN-52021. Gentamicin induced an increase in [Ca2+]i that was inhibited by BN-52021. Gentamicin also stimulated [3H]thymidine incorporation into DNA, an effect that was also reduced by BN-52021, and by other two structurally different PAF receptor antagonists: alprazolam and BB-823. Gentamicin induced c-fos mRNA expression in quiescent mesangial cells. Gentamicin stimulated the synthesis and release of PAF in cultured rat mesangial cells. The present studies demonstrate that gentamicin activates mesangial cell function. These actions seem to be mediated, at least in part, by PAF synthesis and release.