Document Detail

Evidence for physiological functions of protein phosphatases in the heart: evaluation with okadaic acid.
MedLine Citation:
PMID:  8393625     Owner:  NLM     Status:  MEDLINE    
Okadaic acid exerts a positive inotropic effect in cardiac preparations. We studied whether the positive inotropic effect of okadaic acid in cardiac preparations could be due to phosphatase inhibition and whether this inhibition affects the phosphorylation of cardiac proteins. In papillary muscles from guinea pigs, 30 microM okadaic acid increased force of contraction to 175% of predrug value. In isolated guinea pig ventricular cardiomyocytes, okadaic acid augmented single Ca(2+)-channel currents by enhancing channel availability. In homogenates from ventricles, 1 microM okadaic acid completely inhibited phosphorylase a phosphatase activity. In isolated 32P-labeled ventricular cardiomyocytes, 30 microM okadaic acid increased phosphorylation of phospholamban (PLB) and troponin inhibitor (TnI) to 325 and 284% of control, respectively. Furthermore, 30 microM okadaic acid increased phosphorylation of a hitherto unknown 23-kDa protein to 352% of control. It is concluded that the effects of okadaic acid could be mediated by increasing the phosphorylation state of several proteins including PLB, a 23-kDa protein, and TnI.
J Neumann; P Boknik; S Herzig; W Schmitz; H Scholz; R C Gupta; A M Watanabe
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of physiology     Volume:  265     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1993 Jul 
Date Detail:
Created Date:  1993-08-27     Completed Date:  1993-08-27     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  H257-66     Citation Subset:  IM    
Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany.
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MeSH Terms
Calcium-Binding Proteins / metabolism
Cell Separation
Ethers, Cyclic / pharmacology*
Guinea Pigs
Isoproterenol / pharmacology
Myocardial Contraction / drug effects
Myocardium / cytology,  enzymology*
Okadaic Acid
Phosphoprotein Phosphatases / metabolism,  physiology*
Phosphoproteins / metabolism
Phosphorylation / drug effects
Reg. No./Substance:
0/Calcium-Binding Proteins; 0/Ethers, Cyclic; 0/Phosphoproteins; 0/phospholamban; 7683-59-2/Isoproterenol; 78111-17-8/Okadaic Acid; EC Phosphatases

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