Binding of tritiated and radioiodinated ZM241,385 to brain A2A adenosine receptors

Sihver, Wiebke; Bier, Dirk; Holschbach, M.; Schulze, Annette; Wutz, Walter; Olsson, Ray A.; Coenen, Heinz H.

doi:10.1016/j.nucmedbio.2003.10.007

Cited by 15 publications

(7 citation statements)

References 11 publications

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“…This localization of receptors has been shown via immunohistochemical methods (A 2A receptor -see Rosin et al, 1998 ;mGlu5 receptor -see Shigemoto et al, 1993), and autoradiographic methods (mGlu5 receptor -see Patel et al, 2003 ; A 2A receptor -see Sihver et al, 2004). Coimmunoprecipitation of receptor complexes from both transfected cell cultures and rat striatal extracts suggests the existence of mGlu5-A 2A receptor heterodimers (Ferre et al, 2002).…”

Section: Introductionmentioning

confidence: 78%

Combined antagonism of glutamate mGlu5 and adenosine A2A receptors interact to regulate alcohol-seeking in rats

Adams

Cowen

Short

et al. 2007

Int. J. Neuropsychopharm.

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Adenosine and glutamate have been implicated as mediators involved in the self-administration of alcohol. In the present study we sought to determine whether adenosine receptors could interact with metabotropic glutamate receptors to regulate operant responding for alcohol and also the integration of the salience of alcohol-paired cues. Alcohol-preferring (iP) rats were trained to self-administer alcohol under operant conditions. The availability of alcohol was paired with an olfactory cue plus a stimulus light. Rats were examined under fixed ratio responding and also following extinction under a cue-induced reinstatement paradigm. Administration of the selective adenosine A2A receptor antagonist, SCH 58261, reduced fixed ratio responding for alcohol in iP rats in a dose-related manner. Furthermore, the combination of a subthreshold dose of SCH 58261 with a subthreshold dose of the mGlu5 receptor antagonist MTEP also reduced alcohol self-administration and increased the latency to the first reinforced response, suggesting a pre-ingestive effect. Moreover, this combination of SCH 58261 and MTEP also prevented the conditioned reinstatement of alcohol-seeking elicited by the re-presentation of cues previously paired with alcohol availability. In contrast, combinations of the selective adenosine A1 receptor antagonist, DPCPX, with either SCH 58261 or MTEP had no effect on alcohol responding. Collectively, these data suggest a functional interaction between adenosine A2A and mGlu5 receptors in relation to alcohol-seeking and the integration of the drug-related cues.

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Section: Introductionmentioning

confidence: 78%

Combined antagonism of glutamate mGlu5 and adenosine A2A receptors interact to regulate alcohol-seeking in rats

Adams

Cowen

Short

et al. 2007

Int. J. Neuropsychopharm.

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“…The labelled compound eluted in the 50 % methanol fraction. Fresh frozen brain tissue was collected from five mice (Animal Resource Centre, USA) for use in autoradiography studies using protocols adapted from those described previously (Halldner et al 2004 ;Shiver et al 2004 ;Thomas et al 2000). Briefly, alternating serial coronal 14-mm sections were pre-incubated in 50 mM Tris-HCl buffer (pH 7.4, RT) for 10 min before a 90-min assay with 0.05 nM [ 125 I]ZM241385 in buffer (RT).…”

Section: Autoradiographymentioning

confidence: 99%

mGlu5 and adenosine A2A receptor interactions regulate the conditioned effects of cocaine

Brown

Duncan

Stagnitti

et al. 2011

Int. J. Neuropsychopharm.

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Adenosine A2A receptors and metabotropic glutamate type 5 (mGlu5) receptors are co-localized in the striatum and can functionally interact to regulate drug-seeking. We further explored this interaction using antagonism of mGlu5 receptors with 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP) in combination with genetic deletion of A2A receptors. The conditioned rewarding and locomotor-activating properties of cocaine were evaluated via conditioned place preference (CPP). Vehicle-treated mice of both genotypes expressed a CPP to cocaine while MTEP abolished cocaine CPP in wild-type, but not A2A knockout, mice. These results were mirrored when conditioned hyperactivity was assessed. In contrast, MTEP attenuated the acute locomotor-activating properties of cocaine similarly in both genotypes. These data provide evidence for a functional interaction between adenosine A2A and mGlu5 receptors in mediating the conditioned effects of cocaine but not direct cocaine-induced hyperactivity. This functional interaction is supported by modulation of 4-(2-[7-amino-2-[2-furyl][1,2,4]triazolol[2,3-a][1,3,5]triazin-5-yl-amino]ethyl)phenol ([125I]ZM241385) binding to the A2A receptor by MTEP.

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“…It is now used as a radioligand for A 2A AR binding studies [82][83][84]. On this basis, other 6:5 fused heteroaromatic compounds possessing [1,2,4]triazolo[2,3-a] [1,3,5]triazine skeleton were developed to improve its biological properties [68,85].…”

Section: A 2a Ar Xanthine Antagonistsmentioning

confidence: 99%

Potent Adenosine A1 and A2A Receptors Antagonists: Recent Developments

Yuzlenko

Kieć‐Kononowicz

2006

CMC

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This review summarizes the current tendencies observed in the past 5 years in the development of A(1) and A(2A) adenosine receptor antagonists performed in various academia and industry. A(1) and A(2A) AR antagonists are as well xanthines as heteroaromatic derivatives and are most commonly 6:5 fused heteroatomic compounds. Among xanthine-based compounds, some common features could be pointed out. The recent A(1) AR ligands which show good biological profile, possess long alkyl chains in position 1 and 3 as well as bulky C(8)-substituent, while A(2A) AR antagonists with a high A(2A) AR affinity are C(8)-styryl substituted with N(1)-alkyl/alkynyl moiety or fused tricyclic xanthines possessing heteroatom(s) in the third cycle. The research in the field of heteroaromatic A(1) and A(2A) ARs antagonists impressively has a wide range. Ligands are as well non-fused monocyclic substituted compounds as fused bi- and tricyclic derivatives with the nitrogen, oxygen and sulfur heteroatoms. Most often, adenosine A(1) receptor non-xanthine antagonists are adenine-based, having substituted amino group and variable nitrogen atoms positions in the molecules. A(2A) AR ligands show good affinity when furanyl function, which is crucial for binding, is present in the fused bicyclic and tricyclic analogs. Moreover, tricyclic nitrogen containing antagonists in order to be active, frequently possess long-alkylphenyl moiety.

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Binding of tritiated and radioiodinated ZM241,385 to brain A2A adenosine receptors

Cited by 15 publications

References 11 publications

Combined antagonism of glutamate mGlu5 and adenosine A2A receptors interact to regulate alcohol-seeking in rats

Combined antagonism of glutamate mGlu5 and adenosine A2A receptors interact to regulate alcohol-seeking in rats

mGlu5 and adenosine A2A receptor interactions regulate the conditioned effects of cocaine

Potent Adenosine A1 and A2A Receptors Antagonists: Recent Developments

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