Gentamicin activates rat mesangial cells. A role for platelet activating factor.
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.
Rodriguez-Barbero
A
A
Instituto Reina Sofia de Investigaciones Nefrológicas, Departamento de Fisiología y Farmacología, Facultad de Medicina, Universidad de Salamanca, Spain.
Rodriguez-Lopez
A M
AM
Gonzalez-Sarmiento
R
R
López-Novoa
J M
JM
D000525:Alprazolam / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004224:Diterpenes; D016762:Genes, fos / Q000187:drug effects; D005839:Gentamicins / Q000494:pharmacology*; D046934:Ginkgolides; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007783:Lactones / Q000494:pharmacology; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008969:Molecular Sequence Data; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
C094032:BB 823; D004224:Diterpenes; D005839:Gentamicins; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D012333:RNA, Messenger; C045856:ginkgolide B; D007930:Leucine; D002118:Calcium; D000525:Alprazolam