Inhibition of a high affinity cyclic AMP phosphodiesterase and relaxation of canine tracheal smooth muscle.
The cyclic nucleotide phosphodiesterase (PDE) activity of canine tracheal smooth muscle (CTS,) was examined. Column chromatography of soluble CTSM-PDE revealed five peaks of activity. One of these peaks (V) was examined further in this study and showed a high affinity for adenosine 3',5'-cyclic monophosphate (Km = 0.63 microM). Seven pharmacological PDE inhibitors were tested for their abilities to inhibit the peak V enzyme and also for their abilities to cause mechanical relaxation of CTSM strips in isolated tissue baths. A strong correlation (P greater than 0.001) between peak V PDE inhibition (-log Ki) and airway muscle relaxation (-log ED50) was found.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D004974:Etazolate / Q000494:pharmacology; D005260:Female; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000201:enzymology / Q000502:physiology*; D013806:Theophylline / Q000494:pharmacology; D014132:Trachea / Q000502:physiology; D014970:Xanthines / Q000494:pharmacology
D014970:Xanthines; C008514:methylxanthine; D002110:Caffeine; D013806:Theophylline; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D004974:Etazolate