Low KmcAMP Phosphodiesterase Isozymes and Modulation of Tone in Vascular, Airway and Gastrointestinal Smooth Muscle

Both cAMP and cGMP are second messengers which mediate a reduction in tone for a variety of smooth muscle relaxants in vascular, airway and gastrointestinal smooth muscle. In recent years, the development of better biochemical purification methods, as well as the identification/discovery of selective inhibitors of cyclic nucleotide phosphodiesterase (PDE) isozymes, have led to a better understanding of the presence and role of PDE isozymes in various tissues. In particular, recent evidence suggests that there are two distinct PDE isozymes which hydrolyze cAMP with a high affinity. One isozyme is sensitive to inhibition by submicromolar concentrations of cGMP and by various cardiotonic agents (referred to as “cGMP inhibitable” or cGi-PDE). The other isozyme is not inhibited by cGMP but is sensitive to inhibition by rolipram and Ro 20-1724 (referred to as Ro-PDE).