| Reducing ischaemia/reperfusion injury through delta-opioid-regulated intrinsic cardiac adrenergic cells: adrenopeptidergic co-signalling. | |
| | |
MedLine Citation:
|
PMID: 19581316 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
|
AIMS: The purpose of this study was to determine whether intrinsic cardiac adrenergic (ICA) cells release calcitonin gene-related peptide (CGRP), exerting synergistic adrenopeptidergic cardioprotection. METHODS AND RESULTS: In situ hybridization coupled with immunostaining demonstrated that ICA cells exclusively expressed CGRP mRNA and co-expressed CGRP and delta-opioid receptor in human and rat left ventricular (LV) myocardium. Radioimmunoassay detected constitutive CGRP release from ICA cells in human and rat hearts. The delta-opioid agonist [D-Pen(25)]-enkephalin (DPDPE) increased CGRP release from ICA cells in denervated rat heart. In an ischaemia/reperfusion rat model, pre-ischaemic treatment with DPDPE reduced infarct size (IS) by 51 +/- 16% (P < 0.01). Co-infusion of beta(2)-adrenergic receptor (beta(2)-AR) and CGRP receptor (CGRP-R) antagonists increased IS by 62 +/- 23% (P < 0.01) compared with saline and abolished DPDPE-initiated IS reduction. Pre-treatment of ICA cell-myocyte co-culture with the beta(2)-AR/CGRP-R antagonists increased myocyte death rate by 24 +/- 4% (P < 0.01) and abolished DPDPE-initiated myocyte protection against hypoxia/reoxygenation (re-O(2)). In the ICA cell-depleted myocyte culture, DPDPE did not confer myocyte protection. Supplementing ICA cell-depleted myocyte culture with beta(2)-AR/CGRP-R agonists reduced hypoxia/re-O(2)-induced myocyte death by 24 +/- 5% (P < 0.01), simulating endogenous neurohormonal effects of ICA cells. Western blot analysis showed that DPDPE markedly increased phosphorylated myocardial Akt levels. This effect was abolished in the presence of beta(2)-AR/CGRP-R blockade. Terminal dUTP nick-end labelling staining analysis of the LV infarct zone demonstrated that DPDPE reduced myocyte apoptosis by 58 +/- 19% (P < 0.05), an effect that was eliminated in the presence of beta(2)-AR/CGRP-R blockade. Finally, echocardiography showed that DPDPE increased LV contractility in a manner dependent on beta-AR/CGRP-R stimulation. CONCLUSION: ICA cells constitute a delta-opioid-regulated adrenopeptidergic paracrine system conferring robust cardioprotection through beta(2)-AR/CGRP-R co-signalling, resulting in the activation of an anti-apoptotic pathway during ischaemia/reperfusion. |
| | |
Authors:
|
Ming-He Huang; Vincent Nguyen; Yewen Wu; Saurabh Rastogi; Charles Y Lui; Yochai Birnbaum; Hui-Qun Wang; David L Ware; Madhu Chauhan; Nisha Garg; Kian-Keong Poh; Lei Ye; Abdul Razakjr Omar; Huay-Cheem Tan; Barry F Uretsky; Kenichi Fujise |
Related Documents
:
|
15853696 - Natriuretic peptide family: new aspects. 3032046 - Thrombin-receptor occupancy initiates a transient increase in camp levels in mitogenica... 1326946 - Activation of neuromedin b-preferring bombesin receptors on rat glioblastoma c-6 cells ... 22672766 - Increased nmda receptor inhibition at an increased sevoflurane mac. 8866246 - 11 beta-hydroxysteroid dehydrogenase activity in the hippocampus: implications for in v... 9555076 - Expression of estrogen receptor alpha and beta transcripts in female monkey hippocampus... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-07-06 |
Journal Detail:
|
Title: Cardiovascular research Volume: 84 ISSN: 1755-3245 ISO Abbreviation: Cardiovasc. Res. Publication Date: 2009 Dec |
Date Detail:
|
Created Date: 2009-11-17 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: England |
Other Details:
|
Languages: eng Pagination: 452-60 Citation Subset: IM |
Affiliation:
|
Cardiology Division, Department of Internal Medicine, University of Texas Medical Branch, 5.106 John Sealy Annex, Galveston, TX 77555-0553, USA. mihuang@utmb.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: MicroRNA-1 downregulation by propranolol in a rat model of myocardial infarction: a new mechanism fo...
Next Document: Changes in white matter as determinant of global functional decline in older independent outpatients...