EFFECT OF DOPAMINE ON ECTO-5'-NUCLEOTIDASE EXPRESSION IN HUMAN GLOMERULAR MESANGIAL CELLS

Ecto-5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) of mesangial cells may be the main source of adenosine within the glom erulus, and thus essential in the regulation of glomerular microcircul ation. c-AMP and c-AMP-stimulating agents were found to induce ecto-5' -nucleotidase of mesangial cells. Dopamine is a catecholamine known to increase c-AMP levels in mesangial cells. We have studied the effect of dopamine on ecto-5'-nucleotidase expression and DNA synthesis of gl omerular mesangial cells in culture. Human mesangial cells were expose d to dopamine in the concentration range from 0.1 muM- to 1 mM, for 6- 72 h. Ecto-5'-nucleotidase activity of human mesangial cells increased from 118.6 +/- 7.7 to 171 +/- 12 nmol/min/mg in a 72 h culture. This effect was time- and dose-dependent. Cycloheximide, an inhibitor of pr otein synthesis did not modify basal 5'-nucleotidase activity but it s uppressed the stimulatory effect of 10 muM dopamine. DNA synthesis of human mesangial cells, studied after exposure of these cells to the sa me concentrations of dopamine used in the 5'-nucleotidase stimulation, was inhibited, being also dose dependent. These results indicate that dopamine induces ecto-5'-nucleotidase and inhibits DNA synthesis of c ultured human mesangial cells. This action of dopamine on glomerular m esangial cells may be important in the regulation of glomerular hemody namics.