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Gentamicin activates rat mesangial cells. A role for platelet activating factor
A Rodriguez-Barbero1, A M Rodriguez-Lopez, R Gonzalez-Sarmiento
1Instituto Reina Sofia de Investigaciones Nefrológicas, Departamento de Fisiología y Farmacología, Facultad de Medicina, Universidad de Salamanca, Spain.
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.
Insights
Gentamicin harms kidney function by activating mesangial cells. This effect is mediated by platelet-activating factor (PAF) synthesis and release, which can be blocked by PAF antagonists.
Area of Science:
- Nephrology
- Cell Biology
- Pharmacology
Background:
- Gentamicin can decrease glomerular filtration rate.
- This decline may involve mesangial cell contraction or vasoactive hormones.
- Platelet-activating factor (PAF) is a potential mediator.
Purpose of the Study:
- To investigate gentamicin's effects on mesangial cell proliferation, contraction, and calcium mobilization.
- To assess the role of PAF in gentamicin-induced mesangial cell activation.
Main Methods:
- Cultured rat mesangial cells were treated with gentamicin.
- Effects on cell surface area, intracellular calcium ([Ca2+]i), and DNA synthesis ([3H]thymidine incorporation) were measured.
- PAF synthesis, release, and c-fos mRNA expression were assessed.
- PAF receptor antagonists (BN-52021, alprazolam, BB-823) were used to block effects.
Main Results:
- Gentamicin reduced mesangial cell surface area, increased [Ca2+]i, and stimulated DNA synthesis.
- These effects were blunted or inhibited by PAF antagonists.
- Gentamicin induced c-fos mRNA expression and stimulated PAF synthesis and release from mesangial cells.
Conclusions:
- Gentamicin activates mesangial cell functions, including proliferation and contraction.
- Platelet-activating factor (PAF) plays a significant role in mediating gentamicin's effects on mesangial cells.
- Targeting PAF may offer a therapeutic strategy to mitigate gentamicin-induced kidney damage.