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  • Title: Correlation between inhibition of a cyclic GMP phosphodiesterase and relaxation of canine tracheal smooth muscle.
    Author: Polson JB, Krzanowski JJ, Szentivanyi A.
    Journal: Biochem Pharmacol; 1985 Jun 01; 34(11):1875-9. PubMed ID: 2988559.
    Abstract:
    Inhibition of partially purified cyclic nucleotide phosphodiesterase activity as well as pharmacologically induced relaxation of respiratory airways smooth muscle was examined to determine whether any correlation between these two effects could be found. The phosphodiesterase in extracts of canine tracheal smooth muscle was chromatographed on a DEAE Bio-Gel A column and eluted with a sodium chloride gradient. The peak I activity hydrolyzed cGMP at a higher rate than cAMP although the apparent Km values for these two cyclic nucleotides were relatively close. Comparison of the Ki values for alkylxanthine inhibitors of peak I activity correlated remarkably well with the EC50 values of the same compounds as relaxants of canine tracheal smooth muscle strips. It is concluded that inhibition of the peak I enzyme may cause accumulation of an intracellular pool of cyclic nucleotide and thus produce or contribute to the muscle relaxant effects that were observed.
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