Adenosine/dopamine interaction: implications for the treatment of Parkinson's disease

Ferré, Sergi; Popoli, Patrizia; Rimondini, R; Müller, Christian; Strömberg, Ingrid; Ögren, Sven Ove; Fuxé, Kjell

doi:10.1016/s1353-8020(00)00063-8

Cited by 125 publications

(97 citation statements)

References 54 publications

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“…Both CPT and MSX-3 produced motor activation at the same doses that selectively counteracted motor depression induced by the A 1 receptor agonist CPA or the A 2A agonist CGS 21680, respectively. This supports previous findings in rodents suggesting that motor activation induced by CPT is because of selective antagonism of central A 1 receptors (Nikodijevic et al, 1990(Nikodijevic et al, , 1991Baumgold et al, 1992;Jacobson et al, 1993;Popoli et al, 1998;Ferré et al, 2001). The present results, however, do not explain the lack of motor activation induced by other A 1 receptor antagonists, such as DPCPX (sometimes referred to as CPX).…”

Section: Discussionsupporting

confidence: 91%

Involvement of Adenosine A1 and A2A Receptors in the Motor Effects of Caffeine after its Acute and Chronic Administration

Karcz-Kubicha¹,

Αντωνίου²,

Terasmaa

et al. 2003

Neuropsychopharmacol

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180

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The involvement of adenosine A 1 and A 2A receptors in the motor effects of caffeine is still a matter of debate. In the present study, counteraction of the motor-depressant effects of the selective A 1 receptor agonist CPA and the A 2A receptor agonist CGS 21680 by caffeine, the selective A 1 receptor antagonist CPT, and the A 2A receptor antagonist MSX-3 was compared. CPT and MSX-3 produced motor activation at the same doses that selectively counteracted motor depression induced by CPA and CGS 21680, respectively. Caffeine also counteracted motor depression induced by CPA and CGS 21680 at doses that produced motor activation. However, caffeine was less effective than CPT at counteracting CPA and even less effective than MSX-3 at counteracting CGS 21680. On the other hand, when administered alone in habituated animals, caffeine produced stronger motor activation than CPT or MSX-3. An additive effect on motor activation was obtained when CPT and MSX-3 were coadministered. Altogether, these results suggest that the motoractivating effects of acutely administered caffeine in rats involve the central blockade of both A 1 and A 2A receptors. Chronic exposure to caffeine in the drinking water (1.0 mg/ml) resulted in tolerance to the motor effects of an acute administration of caffeine, lack of tolerance to amphetamine, apparent tolerance to MSX-3 (shift to the left of its 'bell-shaped' dose-response curve), and true crosstolerance to CPT. The present results suggest that development of tolerance to the effects of A 1 receptor blockade might be mostly responsible for the tolerance to the motor-activating effects of caffeine and that the residual motor-activating effects of caffeine in tolerant individuals might be mostly because of A 2A receptor blockade.

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Section: Discussionsupporting

confidence: 91%

Involvement of Adenosine A1 and A2A Receptors in the Motor Effects of Caffeine after its Acute and Chronic Administration

Karcz-Kubicha¹,

Αντωνίου²,

Terasmaa

et al. 2003

Neuropsychopharmacol

Self Cite

180

189

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“…In fact, in different experimental models of Parkinson's disease, A 2A receptor antagonists potentiate the motor activating effects of L-DOPA or D 2 receptor agonists (for review see ref. 42). Also in agreement, in the rodent dopaminedenervated striatum, local application of a D 2 receptor agonist potently inhibits the increased neuronal activity (compared with the non-denervated striatum) and this effect is counteracted or potentiated with application of A 2A agonists or antagonists, respectively [41].…”

Section: The Antagonistic a 2a -D 2 Intramembrane Recep-tor Interactionmentioning

confidence: 54%

“…These down-to upstate transitions require channels that can be regulated by striatal transmitters acting through GPCRs, such as the interacting A 2A and D 2 receptors in the GABAergic enkephalinergic neurons. In a re- These effects on neurotransmitter release and neuronal excitability are paralleled by effects on motor activity and other behavioral responses, where selective A 2A receptor agonists or antagonists respectively counteract or potentiate the motor activation induced by dopamine D 2 receptor agonists [38][39][40][41][42]. Consequently, we predicted 15 years ago that A 2A receptor antagonists could be useful in Parkinson's disease, especially potentiating the effects of L-dopa or D 2 receptor agonists [43].…”

Section: The Antagonistic a 2a -D 2 Intramembrane Recep-tor Interactionmentioning

confidence: 99%

An Update on Adenosine A2A-Dopamine D2 Receptor Interactions: Implications for the Function of G Protein-Coupled Receptors

Ferré¹,

Quiroz²,

Woods³

et al. 2008

CPD

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Adenosine A2A-dopamine D2 receptor interactions play a very important role in striatal function. A2A-D2 receptor interactions provide an example of the capabilities of information processing by just two different G protein-coupled receptors. Thus, there is evidence for the coexistence of two reciprocal antagonistic interactions between A2A and D2 receptors in the same neurons, the GABAergic enkephalinergic neurons. An antagonistic A2A-D2 intramembrane receptor interaction, which depends on A2A-D2 receptor heteromerization and Gq/11-PLC signaling, modulates neuronal excitability and neurotransmitter release. On the other hand, an antagonistic A2A-D2 receptor interaction at the adenylyl-cyclase level, which depends on Gs/olf-and Gi/o-type V adenylyl-cyclase signaling, modulates protein phosphorylation and gene expression. Finally, under conditions of upregulation of an activator of G protein signaling (AGS3), such as during chronic treatment with addictive drugs, a synergistic A2A-D2 receptor interaction can also be demonstrated. AGS3 facilitates a synergistic interaction between Gs/olf -and Gi/o-coupled receptors on the activation of types II/IV adenylyl cyclase, leading to a paradoxical increase in protein phosphorylation and gene expression upon co-activation of A2A and D2 receptors. The analysis of A2-D2 receptor interactions will have implications for the pathophysiology and treatment of basal ganglia disorders and drug addiction.Key Words: Adenosine A 2A Receptor, Dopamine D 2 Receptor, G Protein-Coupled Receptors, Receptor Heteromers, Striatum, Basal Ganglia Disorders, Drug Addiction. LOCALIZATION OF THE A 2A -D 2 RECEPTOR HETERO-MERApplying a broad definition of "neurotransmitter" [1], adenosine can be considered as an important neurotransmitter in the CNS, which acts through different subtypes of G protein-coupled receptors (GPCRs). From the four cloned adenosine receptors (adenosine A 1 , A 2A , A 2B and A 3 receptors ) , A 1 and A 2A receptors are the main targets for the physiological effects of adenosine in the brain [2]. A 1 receptor is widely distributed in the brain, including the striatum, while A 2A receptor is mostly concentrated in the striatum [2,3]. It is becoming increasingly obvious that the modulatory role of adenosine in the striatum is related to the ability of A 1 and A 2A receptors to heteromerize with themselves and with other GPCRs, such as dopamine, glutamate, cannabinoid and ATP receptors [4][5][6][7][8][9][10][11][12][13][14]. The present review focuses on the role of one particular adenosine receptor heteromer, the one constituted by the A 2A and the dopamine D 2 receptor, which is already having important implications for the treatment of neuropathologies involving the striatum (see below).Striatal medium spiny neurons are GABAergic efferent neurons which constitute more that 95% of the striatal neuronal population. They receive two main afferents, cortical-limbic-thalamic glutamatergic inputs and dopaminergic mesencephalic inputs, from the substantia nigra pars compac...

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“…Considerable evidence indicates that there is a functional interaction between DA and adenosine A 2A receptors in both dorsal and ventral striatal areas (Chen et al, 2001;Hettinger et al, 2001;Svenningsson et al, 1999;Wang et al, 2000). This interaction often has been studied in the context of animal models related to parkinsonism, which typically focus on neostriatal motor functions (Ferré et al, , 2001Hauber et al, 2001;Ishiwari et al, 2007;Jenner, 2003Jenner, , 2005Morelli and Pinna, 2001;Pinna et al, 2005;Svenningsson et al, 1999). In these studies, adenosine A 2A receptor antagonists have been shown to exert effects consistent with antiparkinsonian actions in animal models (Correa et al, 2004;Ferré et al, 1997Ferré et al, , 2001Hauber et al, 2001;Pinna et al, 2005;Wardas et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…This interaction often has been studied in the context of animal models related to parkinsonism, which typically focus on neostriatal motor functions (Ferré et al, , 2001Hauber et al, 2001;Ishiwari et al, 2007;Jenner, 2003Jenner, , 2005Morelli and Pinna, 2001;Pinna et al, 2005;Svenningsson et al, 1999). In these studies, adenosine A 2A receptor antagonists have been shown to exert effects consistent with antiparkinsonian actions in animal models (Correa et al, 2004;Ferré et al, 1997Ferré et al, , 2001Hauber et al, 2001;Pinna et al, 2005;Wardas et al, 2001). Based upon the results of these animal studies, adenosine A 2A receptor antagonists are now being evaluated for their antiparkinsonian effects in human clinical trials (Jenner, 2005).…”

Section: Introductionmentioning

confidence: 99%

Systemic administration of the adenosine A2A agonist CGS 21680 induces sedation at doses that suppress lever pressing and food intake

Mingote

Pereira

Farrar

et al. 2008

Pharmacology Biochemistry and Behavior

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Adenosine A 2A receptors are involved in the regulation of several behavioral functions. Adenosine A 2A antagonists exert antiparkinsonian effects in animal models, and adenosine A 2A agonists suppress locomotion and impair various aspects of motor control. The present experiments were conducted to study the effects of low doses of the adenosine A 2A agonist CGS 21680 on lever pressing, specific parameters of food intake, and sedation. In the first experiment, the effects of CGS 21680 on fixed ratio 5 lever pressing were assessed. In the second experiment, rats were tested in 30 min feeding sessions, and also were observed for drug-induced sedation using a sedation rating scale. CGS 21680 (0.025, 0.05, 0.1 mg/kg IP) produced a dose related suppression of lever pressing, and also reduced the amount of food consumed. The feeding effect was largely dependent upon a slowing of the rate of feeding, and there was only a modest suppression of time spent feeding. Doses of CGS 21680 that suppressed lever pressing and feeding also were associated with sedation/drowsiness. In conjunction with other studies, the present results suggest that sedative effects may play an important role in some of the behavioral effects produced by systemic administration of adenosine A 2A agonists.

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Adenosine/dopamine interaction: implications for the treatment of Parkinson's disease

Cited by 125 publications

References 54 publications

Involvement of Adenosine A1 and A2A Receptors in the Motor Effects of Caffeine after its Acute and Chronic Administration

Involvement of Adenosine A1 and A2A Receptors in the Motor Effects of Caffeine after its Acute and Chronic Administration

An Update on Adenosine A2A-Dopamine D2 Receptor Interactions: Implications for the Function of G Protein-Coupled Receptors

Systemic administration of the adenosine A2A agonist CGS 21680 induces sedation at doses that suppress lever pressing and food intake

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