GENTAMICIN ACTIVATES RAT MESANGIAL CELLS - A ROLE FOR PLATELET-ACTIVATING-FACTOR

Gentamicin-induced decreases in glomerular filtration rate have been a ssociated with a marked decline in the glomerular capillary ultrafiltr ation coefficient which could be mediated by mesangial cell contractio n or release of vasoactive hormones. We studied the effect of gentamic in on mesangial cells proliferation, contraction and Ca2+ mobilization . Moreover, we attempted to assess a possible role of platelet activat ing factor (PAF) as a mediator of the observed effects of gentamicin o n mesangial cells. Gentamicin induced a reduction of planar surface ar ea of cultured rat mesangial cells that was blunted by the PAF-antagon ist, BN-52021. Gentamicin induced an increase in [Ca2+](i) that was in hibited by BN-52021. Gentamicin also stimulated [H-3]thymidine incorpo ration into DNA, an effect that was also reduced by BN-52021, and by o ther two structurally different PAF receptor antagonists: alprazolam a nd BB-823. Gentamicin induced c-fos mRNA expression in quiescent mesan gial cells. Gentamicin stimulated the synthesis and release of PAF in cultured rat mesangial cells. The present studies demonstrate that gen tamicin activates mesangial cell function. These actions seem to be me diated, at least in part, by PAF synthesis and release.