Rolipram increases cyclic GMP content in L-arginine-treated cultured bovine aortic endothelial cells.
Cultured bovine aortic endothelial cells only contain two cyclic nucleotide phosphodiesterases isoforms: PDE II (cyclic GMP stimulated) and PDE IV (rolipram sensitive). The effects of cilostamide or rolipram alone or together, on cyclic AMP and cyclic GMP levels, were measured in indomethacin-treated endothelial cells alone or in the presence of nitric oxide (NO) modulators. In all conditions, cyclic AMP levels were potently increased (8-13-fold) only when PDE II and PDE IV inhibitors were given together. Cyclic GMP levels were not modified by these PDE inhibitors in control and NG-nitro-L-arginine-methyl ester-treated cells. But surprisingly, in L-arginine-treated cells, cyclic GMP content was increased by 42% by rolipram alone, and combination of rolipram with cilostamide resulted in a further increase in cyclic GMP content (to 153% compared to control cells). These results suggest that in presence of the NO synthase substrate (L-arginine), an increase in cyclic AMP level may upregulate the L-arginine/NO/cyclic GMP pathway.
Kessler
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T
Université Louis Pasteur de Strasbourg, Laboratoire de Pharmacologie et Physiopathologie Cellulaires, CNRS URA 0600, Illkirch, France.
Lugnier
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C
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001011:Aorta; D001120:Arginine / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D006152:Cyclic GMP / Q000096:biosynthesis*; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005092:Exonucleases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D020889:Rolipram
D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D015363:Quinolones; D009569:Nitric Oxide; C021294:cilostamide; D001120:Arginine; D000242:Cyclic AMP; D005092:Exonucleases; C022650:spleen exonuclease; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D006152:Cyclic GMP; D020889:Rolipram; D007213:Indomethacin