Tissue distribution of adenosine receptor mRNAs in the rat

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. Al 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.

Differential Effects of Caffeine on Dopamine and Acetylcholine Transmission in Brain Areas of Drug-naive and Caffeine-pretreated Rats

“…It is unlikely that the psychostimulant properties of caffeine are the result of the increase of DA in the PFCX as drugs (antidepressants) known to increase DA in the PFCX but not in the NAc are devoid of psychostimulant properties . Rather than of DA release, the psychostimulant properties of caffeine are likely to be the result of blockade of A 2a receptors in the striatum including the NAc (Dixon et al 1996;Palmer and Stiles 1995). Failure to activate DA transmission might be related to the relatively weak reinforcing properties of caffeine.…”

“…These receptors are widely distributed through the brain (Dixon et al 1996;Lee and Reddington 1986;Palmer and Stiles 1995), adenosine A 1 receptors being present mostly in cortical layers, hippocampus and striatum (Dixon et al 1996;Palmer and Stiles 1995) and A 2a receptors being co-localized with DA receptors in the striatum (Dixon et al 1996;Palmer and Stiles 1995).…”

Role of adenosine A3 receptors on CA1 hippocampal neurotransmission during oxygen–glucose deprivation episodes of different duration

“…Male Wistar rats (Harlan Italy, Udine, Italy; 150-200 g body weight) were killed with a guillotine while under anesthesia with ether, and their hippocampi were rapidly removed and placed in ice-cold oxygenated (95% O 2 , 5% CO 2 ) artificial cerebral spinal fluid (aCSF) of the following composition (mM): NaCl 124, KCl 3.33, KH 2 PO 4 1.25, MgSO 4 2, CaCl 2 2, NaHCO 3 25, and D-glucose 10. Slices (400 μm thick) were cut with a McIlwain tissue chopper (Mickle Laboratory Engineering Co. Ltd., Gomshall, UK) and kept in oxygenated aCSF for at least 1 h at room temperature.…”

“…Of the four adenosine receptor subtypes, the adenosine A 3 receptor is the most recently cloned [2]. A 3 receptors have a widespread distribution in the rat brain [3] and in the hippocampus are preferentially expressed on nerve terminals [4,5]. The expression of A 3 receptors in the brain is lower than that of other adenosine receptor subtypes [6], and the affinity for adenosine, calculated from binding experiments in rat brain membranes (6.5 μM [2]), is lower than that of A 1 [7] and A 2A [8] receptors.…”

Purinergic signalling-evoked intracellular Ca2+ concentration changes in the regulation of chondrogenesis and skeletal muscle formation

“…In the muscle interstitium, adenosine has been reported to appear as the result of nucleotide degradation within the skeletal muscle fibres and released to the extracellular space in response to contractions [45]. Adenosine receptor transcripts have been identified in skeletal muscle homogenates decades ago; a high expression level of A 2A receptor mRNA, moderate signals for A 2B , and no signals for A 1 and A 3 receptors have been reported [46]. Later, A 2A and A 2B receptors were demonstrated in the sarcolemma and cytosol of human skeletal muscle fibres [47].…”