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Title: Distribution and function of adenosine receptors in the rat
Author: Dixon, A. K.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1997
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This thesis describes investigations into the tissue distribution of messenger RNAs encoding the four cloned adenosine receptors in the rat, and aspects of adenosine A1 and A2a receptor function in the rat central nervous system (CNS). Chapter 1 reviews the literature relating to this field, presenting an overview of adenosine metabolism and adenosine receptor classification, distribution and function. In Chapter 2 the distribution of adenosine A2 and A3 receptor gene expression is described. Chapter 3 describes investigations into the possible anatomical association between the adenosine A1 receptor and members of Kir3.0, a subfamily of inwardly rectifying K+ channels. In Chapter 4 adenosine A1 and A2 receptor mediated control of proenkephalin and substance P gene expression in the rat striatum was investigated. In Chapter 5 the results of an investigation into interactions between striatal adenosine A1 and A2a, receptors, is described. Chapter 6 describes work performed on a related project in which a technique was developed to promote the fusion of cortical synaptosomes, thus rendering them amenable to elctrophysiological examination. The fused entities resulting from this procedure were subsequently characterised. In conclusion, the tissue distribution, at the molecular level, of all four cloned adenosine receptors has been defined. Consequently many novel sites of adenosine receptor gene expression have been identified. Also, certain functional effects of the striatal adenosine A2a receptor have been demonstrated for the first time, these include an ability to control the activity of both major striatal output pathways and a modulatory interaction with colocalised adenosine A1 receptors. The latter observations may be of some importance in the development of new therapeutic approaches designed to alleviate the symptoms of Parkinson's disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available