A ROLE FOR PLATELET-ACTIVATING-FACTOR IN ENDOTHELIN-1-INDUCED RAT MESANGIAL CELL-PROLIFERATION

Endothelin-1 stimulated the release of bioassayable platelet-activatin g factor-like material and the incorporation of acetate to PAF in rat mesangial cells, in a dose-dependent manner, with an EC50 of about 10( -9) M. Endothelin-I also stimulated dose dependently [H-3]thymidine in corporation into DNA, protein synthesis and cell growth. The platelet- activating factor antagonists BN-52021 (10(-5) M), and alprazolam (10( -5) M), reduced significantly endothelin-1-stimulated thymidine incorp oration into DNA, protein synthesis and cell growth. Platelet-activati ng factor also stimulated significantly thymidine incorporation into D NA, cell proliferation and protein synthesis. In conclusion, the prese nt results suggest that endothelin-1 induces mesangial cell proliferat ion through a mechanism involving among others, synthesis and release of platelet-activating factor by these cells.