Regulation of rat mesangial cell growth by diadenosine phosphates

The newly recognized human endogenous vasoconstrictive dinucleotides, diadenosine pentaphosphate (APA) and dia-denosine hexaphosphate (AP6A), were tested for growth stimulatory effects in rat mesangial cells (MC). Both AP5A and AP6A stimulated growth in micromolar concentrations. The growth stimulatory effect exceeded that of ATP, a,4-methylene ATP, adenosine 5'-O-(3-thio)triphosphate and UTP. Both diadenosine phosphates potentiated the growth response to platelet-derived growth factor, but not to insu-lin-like growth factor-i. To further elucidate the site of ac-tion in the cell cycle, RNA and protein synthesis were as-sessed. AP5 and AP6A stimulated protein synthesis, but not RNA formation. Furthermore, both agents increased cyto-solic free Ca2 " concentration. It is concluded that APjA and AP6A may play a regulatory role in MC growth as progression factors and possibly modify MC proliferation in glomerular disease. (J. Clin. Invest. 1995. 95:2862-2867.) Key words: mesangial cells * diadenosine phosphates PDGF * IGF-1- cytosolic free Ca2