Diadenosine polyphosphates and atrial natriuretic peptide are antiproliferative in rat mesangial cells

Modulation of cell proliferation by vasoactive hormones and growth factors involves also changes in the activity of pH-regulatory transporters. In a p receeding paper (1) we examined the influence of such factors on cellular p H(i). Here the influence of the same factors, diadenosine polyphosphates (A pnA), atrial natriuretic peptide, the growth factor PDGF and the Ca2+-ATPas e inhibitor thapsigargin, on proliferation of cultured rat mesangial cells was examined by quantification of [H-3]-thymidine incorporation. Mesangial cells were synchronised and growth reduced (0.5% FCS for 24 h) before exper iments were started. Incubation with Ap3A, Ap4A, Ap5A or Ap6A (all 10 mu M) for 24 h all reduced cell proliferation by 30 to 45%. At 0.1 and 1 mu M th e effects of Ap4A, Ap5A and Ap6A did not reach significance. The antimitoge nic effect of Ap5A was not significantly different when cells were incubate d for 24, 48 or 72 h. In addition there was no significant difference betwe en the antiproliferative effect of Ap5A in cells of the second, sixth or th irteenth passage. The growth factor PDGF-BB (0.25 nM) resulted in an approx imately 3-fold increase in [H-3]-thymidine incorporation. This increase in proliferation could be significantly reduced by coincubation with 10 CIM Ap 5A, The mitogenic effect of PDGF was completely abolished in the presence o f the Ca2+-ATPase inhibitor thapsigargin (1 nM), which also significantly r educed basal cell proliferation by approximately 40%. Incubation of mesangial cells with 10 nM ANP for 24 h reduced basal [H-3]-t hymidine incorporation slightly by approximately 20% and decreased the PDGF -induced stimulation. The antimitogenic effects of these agonists is especi ally pronounced when cells are stimulated. Copyright (C) 2000 S. Karger AG, Basel.