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Role of adenosine A2A receptors in parkinsonian motor impairment and l-DOPA-induced motor complications.
Prog Neurobiol. 2007 Dec; 83(5):293-309.PN

Abstract

Adenosine A2A receptors have a unique cellular and regional distribution in the basal ganglia, being particularly concentrated in areas richly innervated by dopamine such as the caudate-putamen and the globus pallidus. Adenosine A2A receptors are selectively located on striatopallidal neurons and are capable of forming functional heteromeric complexes with dopamine D2 and metabotropic glutamate mGlu5 receptors. Based on the unique cellular and regional distribution of this receptor and in line with data showing that A2A receptor antagonists improve motor symptoms in animal models of Parkinson's disease (PD) and in initial clinical trials, A2A receptor antagonists have emerged as an attractive non-dopaminergic target to improve the motor deficits that characterize PD. Experimental data have also shown that A2A receptor antagonists do not induce neuroplasticity phenomena that complicate long-term dopaminergic treatments. The present review provides an updated summary of results reported in the literature concerning the biochemical characteristics and basal ganglia distribution of A2A receptors. We subsequently aim to examine the effects of adenosine A2A antagonists in rodent and primate models of PD and of l-DOPA-induced dyskinesia. Finally, concluding remarks are made on post-mortem human brains and on the translation of adenosine A2A receptor antagonists in the treatment of PD.

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Authors+Show Affiliations

Morelli M
University of Cagliari, Department of Toxicology, Via Ospedale 72, 09124 Cagliari, Italy. morelli@unica.it
Di Paolo T
No affiliation info available
Wardas J
No affiliation info available
Calon F
No affiliation info available
Xiao D
No affiliation info available
Schwarzschild MA
No affiliation info available

MeSH

Adenosine A2 Receptor AntagonistsAnimalsAntiparkinson AgentsBasal GangliaDisease Models, AnimalDyskinesia, Drug-InducedHumansLevodopaParkinson DiseaseReceptor, Adenosine A2AReceptor, Metabotropic Glutamate 5Receptors, Dopamine D2Receptors, Metabotropic Glutamate

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

17826884

Citation

Morelli, Micaela, et al. "Role of Adenosine A2A Receptors in Parkinsonian Motor Impairment and l-DOPA-induced Motor Complications." Progress in Neurobiology, vol. 83, no. 5, 2007, pp. 293-309.
Morelli M, Di Paolo T, Wardas J, et al. Role of adenosine A2A receptors in parkinsonian motor impairment and l-DOPA-induced motor complications. Prog Neurobiol. 2007;83(5):293-309.
Morelli, M., Di Paolo, T., Wardas, J., Calon, F., Xiao, D., & Schwarzschild, M. A. (2007). Role of adenosine A2A receptors in parkinsonian motor impairment and l-DOPA-induced motor complications. Progress in Neurobiology, 83(5), 293-309.
Morelli M, et al. Role of Adenosine A2A Receptors in Parkinsonian Motor Impairment and l-DOPA-induced Motor Complications. Prog Neurobiol. 2007;83(5):293-309. PubMed PMID: 17826884.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of adenosine A2A receptors in parkinsonian motor impairment and l-DOPA-induced motor complications. AU - Morelli,Micaela, AU - Di Paolo,Therese, AU - Wardas,Jadwiga, AU - Calon,Frederic, AU - Xiao,Danqing, AU - Schwarzschild,Michael A, Y1 - 2007/07/27/ PY - 2007/02/21/received PY - 2007/05/18/revised PY - 2007/07/19/accepted PY - 2007/9/11/pubmed PY - 2008/2/5/medline PY - 2007/9/11/entrez SP - 293 EP - 309 JF - Progress in neurobiology JO - Prog Neurobiol VL - 83 IS - 5 N2 - Adenosine A2A receptors have a unique cellular and regional distribution in the basal ganglia, being particularly concentrated in areas richly innervated by dopamine such as the caudate-putamen and the globus pallidus. Adenosine A2A receptors are selectively located on striatopallidal neurons and are capable of forming functional heteromeric complexes with dopamine D2 and metabotropic glutamate mGlu5 receptors. Based on the unique cellular and regional distribution of this receptor and in line with data showing that A2A receptor antagonists improve motor symptoms in animal models of Parkinson's disease (PD) and in initial clinical trials, A2A receptor antagonists have emerged as an attractive non-dopaminergic target to improve the motor deficits that characterize PD. Experimental data have also shown that A2A receptor antagonists do not induce neuroplasticity phenomena that complicate long-term dopaminergic treatments. The present review provides an updated summary of results reported in the literature concerning the biochemical characteristics and basal ganglia distribution of A2A receptors. We subsequently aim to examine the effects of adenosine A2A antagonists in rodent and primate models of PD and of l-DOPA-induced dyskinesia. Finally, concluding remarks are made on post-mortem human brains and on the translation of adenosine A2A receptor antagonists in the treatment of PD. SN - 0301-0082 UR - https://www.unboundmedicine.com/medline/citation/17826884/Role_of_adenosine_A2A_receptors_in_parkinsonian_motor_impairment_and_l_DOPA_induced_motor_complications_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0301-0082(07)00132-3 DB - PRIME DP - Unbound Medicine ER -