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Comparison of the effects of selective inhibitors of phosphodiesterase types III and IV in airway smooth muscle with differing β‐adrenoceptor subtypes
Author(s) -
Tomkinson Adrian,
Karlsson JanAnders,
Raeburn David
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13439.x
Subject(s) - rolipram , isoprenaline , guinea pig , methacholine , phosphodiesterase , salbutamol , medicine , endocrinology , chemistry , phosphodiesterase inhibitor , bronchus , potency , bronchodilatation , pharmacology , biology , lung , enzyme , biochemistry , in vitro , respiratory disease , stimulation , asthma
1 The relaxant properties of the type IV adenosine 3′,5′‐cyclic monophosphate phosphodiesterase (cyclic AMP PDE) inhibitor, rolipram and the β 2 ‐selective and non‐selective β‐adrenoceptor agonists salbutamol and isoprenaline, were compared on the guinea‐pig, bovine, and mouse trachea and porcine bronchus all precontracted with methacholine (EC 30 ). 2 Rolipram and both β‐agonists produced concentration‐dependent reversal of the methacholine‐induced tone in the four airway preparations. 3 Isoprenaline and salbutamol were similar in potency on the guinea‐pig (−log 10 IC 50 :8.43, 8.06) and bovine (−log 10 IC 50 :8.52, 8.40) airways. In contrast, salbutamol was much less potent than isoprenaline on the mouse trachea (> 1000 fold) and the porcine bronchus (> 100 000 fold). 4 The potency of rolipram approached that of isoprenaline on the guinea‐pig and bovine trachea (β 2 ‐adrenoceptors predominate). However, rolipram was significantly less active than isoprenaline on the porcine bronchus (1000 fold) and mouse trachea (> 2000 fold) where β 2 ‐adrenoceptors predominate. 5 Siguazodan, the type III cyclic AMP PDE inhibitor, produced concentration‐dependent relaxations of the porcine bronchus and guinea‐pig trachea contracted with methacholine. Siquazodan was 100 fold more active than rolipram in pig tissues indicating the type III isoenzyme may be of greater functional significance in this tissue. In contrast, siguazodan was 15 times less potent that rolipram in guinea‐pig airways suggesting a greater role for the type IV PDE. 6 These findings may reflect a possible relationship between the β 2 ‐adrenoceptor subtype and the functional importance of the type IV PDE isoenzyme. A similar relationship may exist between β 1 ‐adrenoceptors and the PDE type III isoenzyme.