The identification of apparently novel cyclic AMP and cyclic GMP phosphodiesterase activities in guinea-pig tracheal smooth muscle.
Phosphodiesterase (PDE) activities that were capable of hydrolysing cyclic AMP (Km = 6.8 +/- 2 microM) and cyclic GMP (Km = 6.7 +/- 1.6 microM) were isolated from tracheal smooth muscle. These enzyme(s) activities were insensitive to stimulation by calcium/calmodulin and to inhibition by cyclic GMP, rolipram (type IV inhibitor) and siguazodan (type III inhibitor). Zaprinast was a relatively poor inhibitor of both cyclic AMP and cyclic GMP hydrolysis (IC50 = 46 +/- 9 microM and 45 +/- 14 microM respectively). These results suggest that tracheal smooth muscle may contain an apparently novel PDE. However, KCl (30 mM) which facilitates calcium entry in cells, depressed bradykinin-stimulated intracellular cyclic AMP formation, suggesting that the type I PDE may be functionally present. We suggest that considerable caution be exercised in identifying apparently novel PDE isoforms.
Burns
F
F
Department of Physiology and Pharmacology, Strathclyde University, Glasgow.
Stevens
P A
PA
Pyne
N J
NJ
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000032:analysis* / Q000037:antagonists & inhibitors; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000032:analysis* / Q000037:antagonists & inhibitors; D000818:Animals; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000032:analysis* / Q000037:antagonists & inhibitors; D009130:Muscle, Smooth / Q000201:enzymology*; D011189:Potassium Chloride / Q000494:pharmacology; D014132:Trachea / Q000201:enzymology*
D007527:Isoenzymes; D011189:Potassium Chloride; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D001920:Bradykinin