Effect of theophylline and other drugs on rabbit renal cyclic nucleotide phosphodiesterase, 5'-nucleotidase and adenosine deaminase.

The effect of theophylline and several other drugs on cyclic AMP and cyclic GMP phosphodiesterase, 5′-nucleotidase and adenosine deaminase was tested in homogenates of rabbit renal cortex and medulla.Theophylline was a competitive inhibitor of cyclic nucleotide phosphodiesterase, a non-competitive inhibitor of 5′-nucleotidase and alkaline phosphatase but did not influence adenosine deaminase. Cyclic AMP and cyclic GMP hydrolysis were inhibited to an equal extent by theophylline, furosemide, caffeine, 3-isobutyl-methylxanthine, and SQ 20006. Dipyridamol, ZK 62.711, Ro 20-1724 and ICI 63.197 inhibited cyclic AMP hydrolysis in at least ten times lower concentrations than cyclic GMP hydrolysis. Conversely, M &; B 22948 and dilazep were more potent as inhibitors of cyclic GMP than of cyclic AMP hydrolysis.All the diuretic agents tested (furosemide, ethacrynic acid, chlorthalidone, cyclopentiazide and theophylline) inhibited 5′-nucleotidase at 1 mM concentration or lower.Of the drugs tested at 1 mM concentration only dipyridamol and chlorthalidone produced significant (30 per cent) inhibition of adenosine deaminase activity.