| The role of beta-adrenergic receptor signaling in cardioprotection. | |
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MedLine Citation:
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PMID: 15802488 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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This study examines the role of the beta2-adrenergic receptor (beta2-AR) in cardioprotection. The beta2-AR couples to Gs and Gi proteins. Gs activates PKA, which phosphorylates the receptor and switches beta2-AR coupling from Gs to Gi. Prior to 20 min of global ischemia, mouse hearts were either perfused for 30 min without treatment (control), treated with 10 nmol/L of isoproterenol (ISO) for 5 min followed by 5 min washout, or preconditioned with 4 cycles of 5 min ischemia and 5 min reflow (PC). Recovery of left ventricular developed pressure (LVDP) and infarct size were measured. Intermittent ISO treatment improved post-ischemic recovery of LVDP (58.5+/-4.8% vs. 22.0+/-6.3% in control) and reduced infarct size (31.0+/-2.4% vs. 53.0+/-4.6% in control). The Gi inhibitor pertussis toxin blocked the ISO-induced improvement in postischemic LVDP and infarct size. To test the role of beta2-AR in PC, we studied mice lacking beta2-AR (beta2-AR-/-) and found that PC had no effect on postischemic LVDP or infarct size in beta2-AR-/-. To test whether PKA is required for the PC and ISO-induced protection, hearts were treated with the PKA inhibitors PKI and H-89. We found that PKI and H-89 blocked the PC- and ISO-induced improvement in postischemic LVDP and infarct size. These data show an important role for beta2-AR in cardioprotection and support the novel hypothesis that preconditioning involves switching of beta2-AR coupling from Gs to Gi. |
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Authors:
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Haiyan Tong; Daniel Bernstein; Elizabeth Murphy; Charles Steenbergen |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S. Date: 2005-03-31 |
Journal Detail:
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Title: FASEB journal : official publication of the Federation of American Societies for Experimental Biology Volume: 19 ISSN: 1530-6860 ISO Abbreviation: FASEB J. Publication Date: 2005 Jun |
Date Detail:
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Created Date: 2005-05-30 Completed Date: 2006-02-17 Revised Date: 2012-06-26 |
Medline Journal Info:
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Nlm Unique ID: 8804484 Medline TA: FASEB J Country: United States |
Other Details:
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Languages: eng Pagination: 983-5 Citation Subset: IM |
Affiliation:
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Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cardiotonic Agents / pharmacology Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors, physiology GTP-Binding Protein alpha Subunits, Gi-Go / antagonists & inhibitors, physiology GTP-Binding Protein alpha Subunits, Gs / antagonists & inhibitors, physiology Ischemia Ischemic Preconditioning, Myocardial Isoproterenol / pharmacology Male Mice Mice, Knockout Mice, Transgenic Myocardial Infarction / physiopathology, prevention & control* Pertussis Toxin / pharmacology Protein Kinase Inhibitors / pharmacology Receptors, Adrenergic, beta-2 / deficiency, physiology* Signal Transduction / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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HL-39752/HL/NHLBI NIH HHS; HL-51535/HL/NHLBI NIH HHS; R01 HL039752/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cardiotonic Agents; 0/Protein Kinase Inhibitors; 0/Receptors, Adrenergic, beta-2; 7683-59-2/Isoproterenol; EC 2.4.2.31/Pertussis Toxin; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases; EC 3.6.5.1/GTP-Binding Protein alpha Subunits, Gi-Go; EC 3.6.5.1/GTP-Binding Protein alpha Subunits, Gs |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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