Volume 118, Issue 6 p. 1461-1468
Free Access

Tissue distribution of adenosine receptor mRNAs in the rat

Alistair K. Dixon

Alistair K. Dixon

Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QJ

Human Genetics Group, The Sanger Centre, Hinxton Hall, Hinxton, Cambs., CB10 1RQ

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Amelie K. Gubitz

Amelie K. Gubitz

Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QJ

Human Genetics Group, The Sanger Centre, Hinxton Hall, Hinxton, Cambs., CB10 1RQ

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Dalip J.S. Sirinathsinghji

Dalip J.S. Sirinathsinghji

Merck Sharpe and Dohme Research Labs, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR

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Peter J. Richardson

Corresponding Author

Peter J. Richardson

Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QJ

Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QJSearch for more papers by this author
Tom C. Freeman

Tom C. Freeman

Human Genetics Group, The Sanger Centre, Hinxton Hall, Hinxton, Cambs., CB10 1RQ

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First published: July 1996
Citations: 456

Abstract

  • 1

    A degree of ambiguity and uncertainty exists concerning the distribution of mRNAs encoding the four cloned adenosine receptors. In order to consolidate and extend current understanding in this area, the expression of the adenosine receptors has been examined in the rat by use of in situ hybridisation and the reverse transcription-polymerase chain reaction (RT-PCR).

  • 2

    In accordance with earlier studies, in situ hybridisation revealed that the adenosine A1 receptor was widely expressed in the brain, whereas A2A receptor mRNA was restricted to the striatum, nucleus accumbens and olfactory tubercle. In addition, A1 receptor mRNA was detected in large striatal cholinergic interneurones, 26% of these neurones were also found to express the A2A receptor gene. Central levels of mRNAs encoding adenosine A2B and A3 receptors were, however, below the detection limits of in situ hybridisation.

  • 3

    The more sensitive technique of RT-PCR was then employed to investigate the distribution of adenosine receptor mRNAs in the central nervous system (CNS) and a wide range of peripheral tissues. As a result, many novel sites of adenosine receptor gene expression were identified. A1 receptor expression has now been found in the heart, aorta, liver, kidney, eye and bladder. These observations are largely consistent with previous functional data. A2A receptor mRNA was detected in all brain regions tested, demonstrating that expression of this receptor is not restricted to the basal ganglia. In the periphery A2A receptor mRNA was also found to be more widely distributed than generally recognised. The ubiquitous distribution of the A2B receptor is shown for the first time, A2B mRNA was detected at various levels in all rat tissues studied. Expression of the gene encoding the adenosine A3 receptor was also found to be widespread in the rat, message detected throughout the CNS and in many peripheral tissues. This pattern of expression is similar to that observed in man and sheep, which had previously been perceived to possess distinct patterns of A3 receptor gene expression in comparison to the rat.

  • 4

    In summary, this work has comprehensively studied the expression of all the cloned adenosine receptors in the rat, and in so doing, resolves some of the uncertainty over where these receptors might act to control physiological processes mediated by adenosine.