REGULATION OF RAT MESANGIAL CELL-GROWTH BY DIADENOSINE PHOSPHATES

The newly recognized human endogenous vasoconstrictive dinucleotides, diadenosine pentaphosphate (AP(5)A) and diadenosine hexaphosphate (AP( 6)A), were tested for growth stimulatory effects in rat mesangial cell s (MC), Both AP(5)A and AP(6)A stimulated growth in micromolar concent rations, The growth stimulatory effect exceeded that of ATP, alpha,bet a-methylene ATP, adenosine 5'-O-(3-thio) triphosphate and UTP, Both di adenosine phosphates potentiated the growth response to platelet-deriv ed growth factor, but not to insulin-like growth factor-1, To further elucidate the site of action in the cell cycle, RNA and protein synthe sis were assessed. AP(5) and AP(6)A stimulated protein synthesis, but not RNA formation, Furthermore, both agents increased cytosolic free C a2+ concentration. It is concluded that AP(5)A and AP(6)A may play a r egulatory role in MC growth as progression factors and possibly modify MC proliferation in glomerular disease.