Document Detail


Antiadrenergic effects of adenosine A(1) receptor-mediated protein phosphatase 2a activation in the heart.
MedLine Citation:
PMID:  12234781     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The ability of adenosine A(1) receptors to activate type 2a protein phosphatase (PP2a) and account for antiadrenergic effects was investigated in rat myocardial preparations. We observed that the adenosine A(1) receptor agonist N(6)-cyclopentyladenosine (CPA) significantly reduces the isoproterenol-induced increase in left ventricular developed pressure of isolated heats, and this effect is blocked by pretreatment of hearts with the PP2a inhibitor cantharidin. CPA alone or given in conjunction with isoproterenol stimulation decreases phosphorylation of phospholamban and troponin I in ventricular myocytes. These dephosphorylations are blocked by an adenosine A(1) receptor antagonist and by PP2a inhibition with okadaic acid. Adenosine A(1) receptor activation was also shown to increase carboxymethylation of the PP2a catalytic subunit (PP2a-C) and cause translocation of PP2a-C to the particulate fraction in ventricular myocytes. These results support the hypothesis that adenosine A(1) receptor activation leads to methylation of PP2a-C and subsequent translocation of the PP2a holoenzyme. Increases in localized PP2a activity lead to dephosphorylation of key cardiac proteins responsible for the positive inotropic effects of beta-adrenergic stimulation.
Authors:
Qinghang Liu; Polly A Hofmann
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  283     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-09-17     Completed Date:  2002-10-17     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1314-21     Citation Subset:  IM    
Affiliation:
Department of Physiology, University of Tennessee School of Medicine, Memphis 38163, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine / analogs & derivatives*,  pharmacology
Adrenergic beta-Agonists / pharmacology
Animals
Calcium-Binding Proteins / metabolism
Cantharidin / pharmacology
Enzyme Inhibitors / pharmacology
Female
Isoproterenol / pharmacology
Methylation
Muscle Fibers, Skeletal / enzymology
Myocardium / cytology,  enzymology*
Okadaic Acid / pharmacology
Phosphoprotein Phosphatases / antagonists & inhibitors,  metabolism*
Phosphorylation
Protein Phosphatase 2
Rats
Rats, Wistar
Receptors, Purinergic P1 / metabolism*
Troponin I / metabolism
Grant Support
ID/Acronym/Agency:
HL-48839/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Adrenergic beta-Agonists; 0/Calcium-Binding Proteins; 0/Enzyme Inhibitors; 0/Receptors, Purinergic P1; 0/Troponin I; 0/phospholamban; 41552-82-3/N(6)-cyclopentyladenosine; 56-25-7/Cantharidin; 58-61-7/Adenosine; 7683-59-2/Isoproterenol; 78111-17-8/Okadaic Acid; EC 3.1.3.16/Phosphoprotein Phosphatases; EC 3.1.3.16/Protein Phosphatase 2

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