Summary of project PR000349

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000349. The data can be accessed directly via it's Project DOI: 10.21228/M8XS4Q This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

Project ID: PR000349
Project DOI:doi: 10.21228/M8XS4Q
Project Title:The alpha-1A adrenergic receptor agonist A61603 reduces cardiac polyunsaturated fatty acid
Project Type:GC-MS non targeted qualitative analysis
Project Summary:Introduction Alpha-1-adrenergic receptors (α1-ARs) are G-protein coupled receptors (GPCRs) with three highly homologous subtypes (α1A, α1B, and α1D). Of these three subtypes, only the α1A and α1B are expressed in the heart. Multiple pre-clinical models of heart injury demonstrate cardioprotective roles for the α1A. Non-selective α1-AR activation promotes glycolysis in the heart, but the functional α1-AR subtype and broader metabolic effects have not been studied. Objectives Given the high metabolic demands of the heart and previous evidence indicating benefit from α1A activation, we chose to investigate the effects of α1A activation on the cardiac metabolome in vivo. Methods Mice were treated for 1 week with a low, subpressor dose of A61603, a highly selective and potent α1A agonist. Cardiac tissue and serum were analyzed using a non-targeted metabolomics approach. Results We identified previously unrecognized metabolic responses to α1A activation,most notably broad reduction in the abundance of polyunsaturated fatty acids(PUFAs) and endocannabinoids (ECs). Conclusion Given the well characterized roles of PUFAs and ECs in inflammatory pathways, these findings suggest a possible role for cardiac α1A-ARs in the regulation of inflammation and may offer novel insight into the mechanisms underlying the cardioprotective benefit of selective pharmacologic α1A activation.
Institute:University of North Carolina at Chapel Hill
Department:McAllister heart Institute, Department of Internal medicine
Laboratory:Multiple Centers
Last Name:Ilaiwy; Willis
First Name:Amro; Monte
Address:111 Mason Farm road, Chapel Hill, North Carolina, 27599-7126, USA
Email:amroilaiwy@gmail.com, monte_willis@med.unc.edu
Phone:210-596-0171
Funding Source:NIH, Fondation Leducq

Summary of all studies in project PR000349

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
Release
Date
VersionSamplesDownload
(* : Contains raw data)
ST000451 The alpha-1A adrenergic receptor agonist A61603 reduces cardiac polyunsaturated fatty acid-Heart raw data Mus musculus University of North Carolina at Chapel Hill MS 2016-09-23 1 16 Not available
ST000452 The alpha-1A adrenergic receptor agonist A61603 reduces cardiac polyunsaturated fatty acid-Serum raw data Mus musculus University of North Carolina at Chapel Hill MS 2016-09-23 1 16 Not available
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