[3H]Cyclohexyladenosine binding in rat brain: A pharmacological analysis using quantitative autoradiography

Snowhill, Elaine W.; Williams, Michael

doi:10.1016/0304-3940(86)90226-0

Cited by 24 publications

(10 citation statements)

References 13 publications

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“…The rather discrete distribution of immunoreactivity for the A 2A subtype in rat brain (predominantly in the striatum) contrasts with the more diffuse presence of immunoreactivity for the A 1 subtype throughout the brain. These differences in patterns of distribution are congruent with A 1 receptor mRNA localization studies (Mahan et al, 1991;Reppert et al, 1991) and radioligand binding studies (Goodman et al, 1983;Snowhill and Williams, 1986;Reppert et al, 1991) and with the distinct neuronal functions ascribed to each of these two receptor subtypes (Fredholm, 1995;Sebastiao and Ribeiro, 1996). In addition to regional variation in receptor distribution, it is conceivable that adenosine receptor subtypes also occupy a segregated anatomical localization at the cellular level.…”

Section: Comparison Of a 2a -And A 1 -Adenosine Receptor Immunolocalisupporting

confidence: 68%

Immunohistochemical localization of adenosine A2A receptors in the rat central nervous system

et al. 1998

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The A2A adenosine receptor (A2A-AR) transcript and radioligand binding sites have a distinct distribution in rat brain, restricted primarily to the striatum, nucleus accumbens and olfactory tubercles. We describe here the use of purified recombinant human A2A-ARs to generate a monoclonal antibody that has been used to better resolve the distribution of A2A-ARs in rat brain. The antibody can detect 1 ng of purified recombinant receptor by Western blotting and is potent (EC50 = 0.62 microg/ml) and highly selective for the A2A-AR subtype. By Western blotting, the apparent molecular mass of recombinant and rat striatal receptors shifts upon deglycosylation from 43-48 to 42 kilodaltons. Analyses of chimeric A1/A2A-ARs and synthesis of a blocking peptide pinpointed the epitope (SQPLPGER) of the antibody to the center of the third intracellular loop of the receptor. Incubation of rat striatal membranes with antibody reduces receptor coupling to G-proteins. In rat brain, dense A2A-AR-like immunoreactivity that is eliminated by the blocking peptide was found in the neuropil of the striatum, nucleus accumbens (rostral pole, core and shell), cell bridges of the striatum, olfactory tubercles, and areas of extended amygdala with somewhat lighter labeling in the globus pallidus and nucleus of the solitary tract. Light perikaryal labeling was found in other areas of the brain, including the cortex, hippocampus, thalamus, cerebellum, and portions of the hindbrain. The observed distribution of A2A-AR immunoreactivity throughout the neuraxis is consistent with the receptors' role in modulating dopaminergic neurotransmission and central control of cardiovascular function.

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Section: Comparison Of a 2a -And A 1 -Adenosine Receptor Immunolocalisupporting

confidence: 68%

Immunohistochemical localization of adenosine A2A receptors in the rat central nervous system

et al. 1998

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“…In contrast to the discrete localization of adenosine A 2A receptors (Jarvis and Williams, 1989;Lupica et al, 1991;Martinez-Mir et al, 1991), A 1 receptors are found throughout the CNS (Goodman and Synder, 1982;Snowhill and Williams, 1986) and relatively homogeneous populations of these receptors are present in micropunches and tissue slices of rat basal ganglia (Mayfield et al, 1996). It is well accepted that in the CNS adenosine acting at A 1 receptors functions as an inhibitory neuromodulator at a number of synapses (Dunwiddie, 1985;Fredholm and Dunwiddie, 1988).…”

Section: Discussionmentioning

confidence: 90%

“…In contrast to the discrete localization of adenosine A 2A receptors, A 1 receptors are widely distributed in brain (Goodman and Synder, 1982;Snowhill and Williams, 1986). Moderate densities of A 1 receptors are present in regions of the basal ganglia, including striatum, globus pallidus, and substantia nigra reticulate, as well as limbic regions such as the nucleus accumbens and olfactory tubercle (Lupica et al, 1991;Mayfield et al, 1996).…”

Section: Introductionmentioning

confidence: 98%

Modulation of endogenous GABA release by an antagonistic adenosine A1 / dopamine D1 receptor interaction in rat brain limbic regions but not basal ganglia

Mayfield

Jones

Miller

et al. 1999

Synapse

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Behavioral and biochemical studies suggest that a negative interaction exists between adenosine A(1) and dopamine D(1) receptors in the brain and that this may contribute to the psychomotor effects of adenosine receptor agonists and antagonists. We examined the functional significance of A(1) and D(1) receptor subtypes in modulating electrically evoked endogenous GABA release from slices/punches of rat basal ganglia (striatum, globus pallidus, striatum containing globus pallidus, and substantia nigra reticulata) and limbic regions (ventral pallidum and nucleus accumbens). In basal ganglia, stimulation of A(1) receptors with the selective agonist R-PIA (1-100 nM) resulted in a concentration-dependent decrease in GABA release. The selective A(1) antagonist DPCPX (10-100 nM) increased GABA release, suggesting that endogenous adenosine tonically inhibits GABA release. However, in basal ganglia, consistent dopamine D(1) receptor modulation of GABA, release was not observed in response to either D(1) agonists or antagonists. Furthermore, the A(1) receptor-mediated inhibition of GABA release was not changed by concurrent activation of D(1) receptors, thus confirming the lack of D(1) receptor modulation under these conditions. In contrast, in ventral pallidum and nucleus accumbens, stimulation of D(1) receptors with SKF-82958 (1 microM) increased GABA release significantly. The D(1) receptor-mediated increase in GABA release was attenuated by concurrent activation of adenosine A(1) receptors. These results are consistent with the hypothesis that an antagonistic A(1)/D(1) receptor interaction may be important in modulating GABA release in limbic regions.

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“…Autoradiography of adenosine A1 receptors was performed according to published methods (Snowhill and Wiliams, 1986; Jarvis et al, 1989; Georgiev et al, 1993). Coronal brain sections of 20 μm were cut on a cryostat microtome and thaw mounted onto gelatin‐coated glass slides.…”

Section: Methodsmentioning

confidence: 99%

Ageing‐related decline in adenosine A1 receptor binding in the rat brain: An autoradiographic study

Meerlo

Román

Farkas

et al. 2004

J of Neuroscience Research

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The adenosine system has important neuromodulatory and neuroprotective functions in the brain. Several lines of evidence suggest that ageing is associated with major alterations in the adenosine system, which may be partially responsible for changes in sleep, mood, and cognition. In the present study, we examined adenosine A1 receptor density in the rat brain by means of quantitative autoradiography to obtain a detailed anatomical overview of the changes during ageing. A1 receptor binding was assessed in young, old, and senescent animals of 3, 24, and 30 months old, respectively. There was a clear age-dependent reduction in adenosine A1 receptors in most of the brain areas examined, but the magnitude of this reduction varied greatly among regions. Also, whereas some regions displayed a gradual decline in A1 binding sites across the three age classes, other regions showed a particularly strong decrease between the ages of 24 and 30 months. For example, whereas the hippocampus and thalamus showed a gradual decline in A1 binding, some cortical and septal regions showed a more abrupt decline after the age of 24 months. Since particularly in rats many studies have used animals at the age of 24 months or even less, the ageing-related decline in adenosine A1 signaling might have been underestimated.

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[3H]Cyclohexyladenosine binding in rat brain: A pharmacological analysis using quantitative autoradiography

Cited by 24 publications

References 13 publications

Immunohistochemical localization of adenosine A2A receptors in the rat central nervous system

Immunohistochemical localization of adenosine A2A receptors in the rat central nervous system

Modulation of endogenous GABA release by an antagonistic adenosine A1 / dopamine D1 receptor interaction in rat brain limbic regions but not basal ganglia

Ageing‐related decline in adenosine A1 receptor binding in the rat brain: An autoradiographic study

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