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The catalytic subunit of protein kinase A triggers activation of the type V cyclic GMP-specific phosphodiesterase from guinea-pig lung

Burns, F and Rodger, I W and Pyne, N J (1992) The catalytic subunit of protein kinase A triggers activation of the type V cyclic GMP-specific phosphodiesterase from guinea-pig lung. Biochemical journal, 283 (2). pp. 487-491. ISSN 0264-6021

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Abstract

The type V cyclic GMP phosphodiesterase was partially purified from the high-speed supernatant of guinea-pig lung. The isoenzyme displayed linear kinetics for cyclic GMP hydrolysis, with Km = 2.2 +/- 0.2 microM and Vmax. = 1.2 +/- 0.08 nmol/min per mg. The selective type V phosphodiesterase inhibitor Zaprinast inhibited cyclic GMP hydrolysis with IC50 (concn. giving 50% inhibition) = 0.45 +/- 0.08 microM. Isobutylmethylxanthine promoted a 3-fold increase in the binding of cyclic GMP to the isoenzyme. The addition of the catalytic subunit of protein kinase A to an activation cocktail containing the partially purified type V phosphodiesterase resulted in a marked increase in Vmax. for cyclic GMP hydrolysis (approximately 10-fold at 40 units of protein kinase A). We have suggested that protein kinase A triggers phosphorylation of the phosphodiesterase, which results in activation of phosphodiesterase activity. In addition, the sensitivity to inhibition by Zaprinast is severely decreased (the IC50 for inhibition is 7.5 +/- 1.1 microM), suggesting that the potency of phosphodiesterase inhibitors is effected by phosphorylation of the enzyme.

Item type: Article
ID code: 34990
Keywords: 3',5'-cyclic-AMP phosphodiesterases, 3',5'-cyclic-GMP phosphodiesterases, animals, chromatography, affinity, chromatography, ion exchange, cytosolic, enzyme activation, guinea pigs, isoenzymes, kinetics, lung, macromolecular substances, protein kinases, purinones, substrate specificity, Pharmacy and materia medica
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
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    Depositing user: Pure Administrator
    Date Deposited: 15 Nov 2011 05:19
    Last modified: 12 Mar 2012 11:37
    URI: http://strathprints.strath.ac.uk/id/eprint/34990

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