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 (K-m = 6.8 +/- 2 mu M) and cyclic GMP (K-m = 6.7 +/- 1.6 mu M) 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 mu M and 45 +/- 14 mu M 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.