TISSUE DISTRIBUTION OF ADENOSINE RECEPTOR MESSENGER-RNAS IN THE RAT

1 A degree of ambiguity and uncertainty exists concerning the distribu tion of mRNAs encoding the four cloned adenosine receptors. In order t o consolidate and extend current understanding in this area, the expre ssion of the adenosine receptors has been examined in the rat by use o f in situ hybridisation and the reverse transcription-polymerase chain reaction (RT-PCR). 2 In accordance with earlier studies, in situ hybr idisation revealed that the adenosine A(1) receptor was widely express ed in the brain, whereas A(2A) receptor mRNA was restricted to the str iatum, nucleus accumbens and olfactory tubercle. In addition, A(1) rec eptor mRNA was detected in large striatal cholinergic interneurones, 2 6% of these neurones were also found to express the A(2A) receptor gen e. Central levels of mRNAs encoding adenosine A(2B) and A(3) receptors were, however, below the detection limits of in situ hybridisation. 3 The more sensitive technique of RT-PCR was then employed to investiga te the distribution of adenosine receptor mRNAs in the central nervous system (CNS) and a wide range of peripheral tissues. As a result, man y novel sites of adenosine receptor gene expression were identified. A (1) receptor expression has now been found in the heart, aorta, liver, kidney, eye and bladder. These observations are largely consistent wi th previous functional data. A(2A) receptor mRNA was detected in all b rain regions tested, demonstrating that expression of this receptor is not restricted to the basal ganglia. In the periphery A(2A) receptor mRNA was also found to be more widely distributed than generally recog nised. The ubiquitous distribution of the A(2B) receptor is shown for the first time, A(2B) mRNA was detected at various levels in all rat t issues studied. Expression of the gene encoding the adenosine A(3) rec eptor was also found to be widespread in the rat, message detected thr oughout the CNS and in many peripheral tissues. This pattern of expres sion is similar to that observed in man and sheep, which had previousl y been perceived to possess distinct patterns of A(3) receptor gene ex pression in comparison to the rat. 4 In summary, this work has compreh ensively studied the expression of all the cloned adenosine receptors in the rat, and in so doing, resolves some of the uncertainty over whe re these receptors might act to control physiological processes mediat ed by adenosine.