Characterization of renal ecto-phosphodiesterase

Edwin K. Jackson, Jin Ren, Lefteris C. Zacharia, Zaichuan Mi

Research output: Contribution to journalArticlepeer-review


In kidneys, stimulation of adenylyl cyclase causes egress of cAMP, conversion of cAMP to AMP by ecto-phosphodiesterase, and metabolism of AMP to adenosine by ecto-5′-nucleotidase. Although much is known about ecto-5′-nucleotidase, the renal ecto-phosphodiesterase remains uncharacterized. We administered cAMP (10 μM in the perfusate) to 12 different groups of perfused kidneys. AMP was measured in perfusate using ion trap mass spectrometry. In control kidneys (n = 19), basal renal secretion rate of AMP was 0.49 ± 0.08 and increased to 3.0 ± 0.2 nmol AMP/g kidney weight/min during administration of cAMP. A broad-spectrum phosphodiesterase (PDE) inhibitor (1,3-isobutyl-1-methylxanthine, 300 μM, n = 6) and an ecto-phosphodiesterase inhibitor (1,3-dipropyl-8-p- sulfophenylxanthine, 1 mM, n = 6) significantly attenuated cAMPinduced AMP secretion by 60 and 74%, respectively. Blockade of PDE1 (8-methoxymethyl-3- isobutyl-1-methylxanthine, 100 μM), PDE2 [erythro-9-(2-hydroxy-3-nonyl) adenine, 30 μM], PDE3 (milrinone, 10 μM; cGMP, 10 μM), PDE4 (Ro 20-1724 [4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one], 100 μM), PDE5 and PDE6 (zaprinast, 30 μM), and PDE7 [BRL-50481 (5-nitro-2,N,N- trimethylbenzenesulfonamide), 10 μM] did not alter renal ecto- phosphodiesterase activity. Administration of a concentration (100 μM) of dipyridamole that blocks PDE8 inhibited ecto-phosphodiesterase activity (by 44%). However, a lower concentration of dipyridamole (3 μM) that blocks PDE9, PDE10, and PDE11, but not PDE8, did not inhibit ecto-phosphodiesterase activity. These data support the conclusion that renal ecto-phosphodiesterase activity is not mediated by PDE1, PDE2, PDE3, PDE4, PDE5, PDE6, PDE7, PDE9, PDE10, or PDE11 and is inhibited by high concentrations of dipyridamole. Ecto-phosphodiesterase has some pharmacological characteristics similar to PDE8.

Original languageEnglish
Pages (from-to)810-815
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number2
Publication statusPublished - May 2007


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