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AJP - Lung Cellular and Molecular Physiology, Vol 264, Issue 5 458-L464, Copyright © 1993 by American Physiological Society
ARTICLES |
K. F. Rabe, H. Tenor, G. Dent, C. Schudt, S. Liebig and H. Magnussen
Krankenhaus Grosshansdorf, Zentrum fur Pneumologie und Thoraxchirurgie, Landesversicherungsanstalt Freie und Hansestadt Hamburg, Federal Republic of Germany.
The effects of the nonselective phosphodiesterase (PDE)-inhibitor 3-isobutyl-1-methylxanthine (IBMX) and the selective PDE inhibitors SKF 94120 (type III), rolipram (type IV), zardaverine (type III/IV), and zaprinast (type V) on inherent tone in human airways were investigated. Substantial relaxation was achieved by IBMX [concentration eliciting 50% of maximum response (EC50): 2.9 microM, n = 14] and SKF 94120 (EC50: 1.4 microM, n = 15); rolipram and zaprinast were almost ineffective. Zardaverine (EC50: 0.31 microM, n = 8), and the combination of SKF 94120 and rolipram (1 microM; EC50: 0.41 microM) were effective relaxants. Biochemical studies revealed the presence of PDE isozymes I, III, IV, and V in the cytosolic and particulate phase of airway homogenates, whereas PDE II was present only in the cytosol. Partial inhibition of total PDE adenosine 3',5'-cyclic monophosphate-hydrolyzing activity was achieved with rolipram and a selective type III inhibitor, whereas there was almost complete inhibition of total PDE activity with either zardaverine or the combination of type III and IV inhibitors. We conclude that all five PDE isozyme families are present in crude preparations of human peripheral airways. Inherent tone in this tissue is most effectively relaxed through selective type III/IV PDE inhibitors.
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