Role of calcium in gentamicin-induced mesangial cell activation.
Gentamicin-induced decreases in glomerular filtration rate have been associated to a marked decline in the glomerular capillary ultrafiltration coefficient which could be due to an active contraction of mesangial cells. In the present work we assessed a possible role of cytosolic Ca2+ as a mediator that leads to contraction and proliferation induced by gentamicin on mesangial 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, TMB8. Gentamicin induced a planar surface area reduction in cultured mesangial cells, that was blunted by verapamil and TMB-8. Gentamicin also stimulated [3H]thymidine incorporation into DNA and increased viable cell number, effects that were reduced 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 mesangial cells. In summary, gentamicin directly raised intracellular Ca2+ activating both calcium influx from external medium and calcium release from internal stores. This increase is responsible of cellular activation (contraction and proliferation) and PAF synthesis induced by gentamicin on mesangial cells.
Martínez-Salgado
C
C
Instituto Reina Sofa de Investigacin Nefrolgica, Departamento de Fisiologa y Farmacologa, Universidad de Salamanca, Salamanca, Spain.
Rodríguez-Barbero
A
A
Tavares
P
P
Eleno
N
N
López-Novoa
J M
JM
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005839:Gentamicins / Q000494:pharmacology*; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017136:Ion Transport; D051381:Rats; D017208:Rats, Wistar; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D005839:Gentamicins; D018808:Transcription Factor AP-1; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D014700:Verapamil; D002118:Calcium