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Mechanisms of β 3 ‐adrenoceptor‐induced eNOS activation in right atrial and left ventricular human myocardium
Author(s) -
Brixius Klara,
Bloch Wilhelm,
Pott Christian,
Napp Andreas,
Krahwinkel Andreas,
Ziskoven Christoph,
Koriller Marco,
Mehlhorn Uwe,
Hescheler J,
Fleischmann Bernd,
Schwinger Robert H G
Publication year - 2004
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705983
Subject(s) - enos , medicine , phosphorylation , endocrinology , protein kinase b , nitric oxide , nitric oxide synthase , chemistry , biology , microbiology and biotechnology
β ‐adrenoceptors are important modulators of cardiac function. The present study investigated β 3 ‐adrenergic eNOS activation in human myocardium. We measured nitric oxide (NO) liberation (diaminofluorescence) and signal transduction (immunohistochemistry, phosphorylation of eNOS Ser1177 , eNOS Thr495 , eNOS Ser114 , Akt/protein kinase B (Akt/PKB), and eNOS translocation) in human right atrial (RA, aortocoronary‐bypass OP) and left ventricular nonfailing (LV, rejected donor hearts) myocardium after application of BRL 37344 (BRL), a preferential β 3 ‐adrenoceptor agonist. In both RA and LV, BRL (10 μ l) induced a liberation of NO. An eNOS activation via translocation was only observed in RA after application of BRL (10 μ M ). Yet, the NO liberation in both LV and RA was accompanied by phosphorylation of eNOS Ser1177 and Akt/PKB. BRL‐induced eNOS phosphorylation was abolished by LY292004, a blocker of PI‐3 kinase. eNOS‐Ser 114 phosphorylation was unchanged in RA, but decreased in LV after β 3 ‐adrenergic stimulation. BRL did not alter phosphorylation of eNOS Thr495 . In conclusion, receptor‐dependent eNOS activation is differentially regulated in the human heart. In the left ventricle, eNOS activation via phosphorylation seems to be of major importance, whereas in human atrial myocardium eNOS translocation is the predominant mechanism induced by β 3 ‐adrenergic activation.British Journal of Pharmacology (2004) 143 , 1014–1022. doi: 10.1038/sj.bjp.0705983