Effect of dipyridamole on glomerular mesangial cell ecto-5'-nucleotidase expression

Although dipyridamole has been extensively studied as an anti-aggregating agent, its mechanism of action has not been elucidated. Cultured mesangial cells were treated with dipyridamole 1-100 microM from 6-72 h. Ecto-5'-nucleotidase activity approximately doubled (from 115 +/- 11 to 226 +/- 14 nmol/min/mg) after treatment with 100 microM dipyridamole for 72 h. This effect was concentration- and time-dependent. Cycloheximide, an inhibitor of protein synthesis, did not alter basal 5'-nucleotidase activity. However, it prevented stimulation by 5 microM dipyridamole. Adenosine availability at the receptor sites was increased by dipyridamole and S-(p-nitrobenzyl)-6-thioinosine (NBTI), which inhibit adenosine uptake into the cell. Addition of dipyridamole or NBTI to the adenosine-treated mesangial cells produced an additive increase in ecto-5'-nucleotidase activity. Dipyridamole, through its effect on extracellular adenosine and ecto-5'-nucleotidase, may have an influence upon regulation of the glomerular microcirculation.