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Adenosine A3 Receptors in Muscle Protection

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Book cover A3 Adenosine Receptors from Cell Biology to Pharmacology and Therapeutics

Abstract

A growing body of evidence has accumulated to indicate an important cyto-protective role of the adenosine A3 receptor. This protective function, originally discovered in ameliorating ischemia–reperfusion injury in the heart, is now also extended to the skeletal muscle. Understanding the pharmacology of various adenosine receptor subtypes allowed their selective activation and delineated the protective role of adenosine A3 receptors as well as that of other receptor subtypes. The use of phospholipase Cβ2/β3 knockout mice showed that the A3 receptor-induced anti-ischemic protection in the skeletal muscle is mediated via this phospholipase isoform. The protective effect of adenosine A1 and A2A receptors, however, does not involve this phospholipase C. Other potential effectors of the adenosine A3 receptor include KATP channels, reactive oxygen species, RISK-reperfusion injury salvage kinase, mPTP-mitochondrial permeability transition pore, matrix metalloproteinases and associated tissue inhibitor of metallproteinases, and metallothionein. Direct muscle protection mediated via muscle cell-surface A3 receptors as well as anti-inflammatory effects exerted at the level of immune cell A3 receptors may contribute to the potent cytoprotective effect of the adenosine A3 receptor.

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Acknowledgements

Kenneth A Jacobson acknowledges support by the Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases. BTL acknowledges support by a grant (W81XWH-05-1-0060) from USAMRMC, Department of Defense. We thank Dr. Moshe Chinn for providing the binding data on MRS1523 in Table 13.1.

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Authors and Affiliations

  1. Pat and Jim Calhoun Cardiovascular Center, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT, 06030, USA

    Bruce T. Liang

  2. Cardiovascular Center, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT, 06030, USA

    Bruce T. Liang

  3. Army Research Institute of Environmental Medicine, Natick, MA, USA

    Maria Urso & Edward Zambraski

  4. Laboratory of Bioorganic Chemistry, NIDDK, NIH, Bethesda, MD, USA

    Kenneth A. Jacobson

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  1. Bruce T. Liang
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  2. Maria Urso
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  4. Kenneth A. Jacobson
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Editors and Affiliations

  1. Ist. Farmacologia, Universita Ferrara, Via Fossato di Mortara 64 B, Ferrara, 44100, Italy

    Pier Andrea Borea

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Liang, B.T., Urso, M., Zambraski, E., Jacobson, K.A. (2010). Adenosine A3 Receptors in Muscle Protection. In: Borea, P. (eds) A3 Adenosine Receptors from Cell Biology to Pharmacology and Therapeutics. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3144-0_13

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