Distribution and function of adenosine receptors in the rat

• Main Author: Dixon, A. K.
• Published: University of Cambridge 1997
• Subjects: 572
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.598553

This thesis describes investigations into the tissue distribution of messenger RNAs encoding the four cloned adenosine receptors in the rat, and aspects of adenosine A<SUB>1</SUB> and A<SUB>2a</SUB> 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 A<SUB>2</SUB> and A<SUB>3</SUB> receptor gene expression is described. Chapter 3 describes investigations into the possible anatomical association between the adenosine A<SUB>1</SUB> receptor and members of Kir3.0, a subfamily of inwardly rectifying K<SUP>+</SUP> channels. In Chapter 4 adenosine A<SUB>1</SUB> and A<SUB>2</SUB> 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 A<SUB>1</SUB> and A<SUB>2a</SUB>, 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 A<SUB>2a</SUB> 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 A<SUB>1</SUB> 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.