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.
Institute of Nephrology and Hemodialysis, Faculty of Medicine, Nis, Yugoslavia.
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Stefanović
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Savić
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Vlahović
D015720:5'-Nucleotidase / Q000378:metabolism*; D000241:Adenosine / Q000494:pharmacology; D000345:Affinity Labels; D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004176:Dipyridamole / Q000494:pharmacology*; D005920:Glomerular Mesangium / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology
D000345:Affinity Labels; D003609:Dactinomycin; D013868:Thioinosine; D004176:Dipyridamole; D003513:Cycloheximide; D015720:5'-Nucleotidase; C001789:4-nitrobenzylthioinosine; D000241:Adenosine