The distribution of adenosine a1 receptors and 5'-nucleotidase in the brain of some commonly used experimental animals

Fastbom, Johan; Pazos, Ángel; Palacios, J.M.

doi:10.1016/0306-4522(87)92961-7

Cited by 294 publications

(131 citation statements)

References 20 publications

Supporting

Mentioning

116

Contrasting

Order By: Relevance

“…Therefore, increased endogenous adenosine levels induced by ABT‐702 may have decreased neuronal activity and decreased energy consumption in the A 1 receptor‐abundant regions. The most significantly affected region was the cerebellum, which is in line with previous studies that demonstrated the highest abundance of adenosine A 1 receptors in rat cerebellum and hippocampus 7, 8. Although not significant at corrected level, a sizable reduction of FDG uptake was also observed in the hippocampus ( P = 0.087).…”

Section: Discussionsupporting

confidence: 89%

The Effect of Endogenous Adenosine on Neuronal Activity in Rats: An FDG PET Study

Parkinson

Paul

Zhang

et al. 2016

Journal of Neuroimaging

View full text Add to dashboard Cite

ABSTRACT2–18F‐fluorodeoxy‐D‐glucose (FDG) is a glucose analog that is taken up by cells and phosphorylated. The amount of FDG accumulated by cells is a measure of the rate of glycolysis, which reflects cellular activity. As the levels and actions of the neuromodulator adenosine are dynamically regulated by neuronal activity, this study was designed to test whether endogenous adenosine affects tissue accumulation of FDG as assessed by positron emission tomography (PET) or by postmortem analysis of tissue radioactivity. Rats were given an intraperitoneal injection of the adenosine A1 receptor antagonist 8‐cyclopentyl‐1,3‐dipropyl‐xanthine (DPCPX, 3 mg/kg), the adenosine kinase inhibitor ABT‐702 (3 mg/kg), or vehicle 10 minutes prior to an intravenous injection of FDG (15.4 ± 0.7 MBq per rat). Rats were then subjected to a 15 minute static PET scan. Reconstructed images were normalized to FDG PET template for rats and standard uptake values (SUVs) were calculated. To examine the regional effect of active treatment compared to vehicle, statistical parametric mapping analysis was performed. Whole‐brain FDG uptake was not affected by drug treatment. Significant regional hypometabolism was detected, particularly in cerebellum, of DPCPX‐ and ABT‐702 treated rats, relative to vehicle‐treated rats. Thus, endogenous adenosine can affect FDG accumulation although this effect is modest in quiescent rats.

show abstract

Section: Discussionsupporting

confidence: 89%

The Effect of Endogenous Adenosine on Neuronal Activity in Rats: An FDG PET Study

Parkinson

Paul

Zhang

et al. 2016

Journal of Neuroimaging

View full text Add to dashboard Cite

show abstract

“…Out of the four adenosine receptors, the A 1 R is the most abundant and widespread in the brain (see, e.g., [5]). A 2A Rs are concentrated in the basal ganglia (reviewed in [6]), but they are also present throughout the brain albeit with a considerably lower density (discussed in BModulatory roles of adenosine^).…”

Section: Adenosine Receptorsmentioning

confidence: 99%

“…Although A 1 Rs are most abundant in limbic and neocortical regions, they are also abundant in the basal ganglia and cerebellum and are also present in most nuclei in the diencephalon and brain stem (see [5] for a detailed mapping of the relative densities of brain A 1 Rs [20]). This probably reflects the general low accessibility of antibodies to extracellular epitopes located in the synaptic cleft, which is densely packed with adhesion molecules [21].…”

Section: Subcellular Localization Of Adenosine Receptorsmentioning

confidence: 99%

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Cunha

2005

Purinergic Signalling

470

427

View full text Add to dashboard Cite

Adenosine is a neuromodulator that operates via the most abundant inhibitory adenosine A 1 receptors (A 1 Rs) and the less abundant, but widespread, facilitatory A 2A Rs. It is commonly assumed that A 1 Rs play a key role in neuroprotection since they decrease glutamate release and hyperpolarize neurons. In fact, A 1 R activation at the onset of neuronal injury attenuates brain damage, whereas its blockade exacerbates damage in adult animals. However, there is a down-regulation of central A 1 Rs in chronic noxious situations. In contrast, A 2A Rs are up-regulated in noxious brain conditions and their blockade confers robust brain neuroprotection in adult animals. The brain neuroprotective effect of A 2A R antagonists is maintained in chronic noxious brain conditions without observable peripheral effects, thus justifying the interest of A 2A R antagonists as novel protective agents in neurodegenerative diseases such as Parkinson's and Alzheimer's disease, ischemic brain damage and epilepsy. The greater interest of A 2A R blockade compared to A 1 R activation does not mean that A 1 R activation is irrelevant for a neuroprotective strategy. In fact, it is proposed that coupling A 2A R antagonists with strategies aimed at bursting the levels of extracellular adenosine (by inhibiting adenosine kinase) to activate A 1 Rs might constitute the more robust brain neuroprotective strategy based on the adenosine neuromodulatory system. This strategy should be useful in adult animals and especially in the elderly (where brain pathologies are prevalent) but is not valid for fetus or newborns where the impact of adenosine receptors on brain damage is different.Abbreviations: Ab -b-amyloid peptide; A 1 Rs -A 1 receptors; A 2A Rs -A 2A

show abstract

“…These results suggest region-, age-, and gender-dependent functions of nucleosides in the human brain. Correlations have been observed between the (1) S -(4-nitrobenzyl)-6-thioinosine (NBTI) binding site and the density of adenosine deaminase (ADA) immunoreactive neurons (Geiger and Nagy 1986 ) , (2) regional differences in nucleoside levels and the nucleoside metabolic enzyme activities and distribution of adenosine receptors (Kovács et al 2010a ) , (3) ENT1 subtype of equilibrative nucleoside transporters (ENT1) and A 1 adenosine receptor subtype (A 1 R) density (Jennings et al 2001 ) , and (4) A 1 R density and 5 ¢ -nucleotidase (5 ¢ NTs) levels (Fastbom et al 1987 ) . Interactions have also been observed between ADA and A 1 Rs, resulting in the facilitation of agonist binding to A 1 Rs and the enhancement of receptor functionality in the human caudate nucleus (Gracia et al 2008 ) .…”

Section: Introductionmentioning

confidence: 99%

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

Kovács

Dobolyi

2012

Adenosine

View full text Add to dashboard Cite

Nucleosides have a wide range of physiological and pathophysiological roles in the human brain as modulators of a variety of neural functions. For example, adenosine, inosine, guanosine, and uridine participate in the mechanisms underlying memory, cognition, sleep, pain, depression, schizophrenia, epilepsy, Alzheimer's disease, Huntington's disease, and Parkinson's disease. Consequently, increasing attention is now being given to the speci fi c role of nucleosides in physiological and pathological processes in the human brain. Different elements of nucleoside system, including nucleoside concentrations, metabolic enzyme activity, and expression of nucleoside transporters and receptors, may be changed under normal and pathological conditions. The alterations suggest that interlinked elements of the nucleoside system are functioning in a tightly concerted manner.Nucleoside levels, activity of nucleoside metabolic enzymes, and expression of nucleoside transporters and receptors are unevenly distributed in the brain, suggesting that nucleosides have different roles in functionally distinct human brain areas. The aim of this chapter is to summarize our present knowledge of the anatomical distribution of nucleoside system in the human brain, placing emphasis on potential therapeutic pharmacological strategies.

show abstract

The distribution of adenosine a1 receptors and 5'-nucleotidase in the brain of some commonly used experimental animals

Cited by 294 publications

References 20 publications

The Effect of Endogenous Adenosine on Neuronal Activity in Rats: An FDG PET Study

The Effect of Endogenous Adenosine on Neuronal Activity in Rats: An FDG PET Study

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

Contact Info

Product

Resources

About