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Articles
December 8, 2003

Receptor heteromerization in adenosine A2A receptor signaling
Relevance for striatal function and Parkinson’s disease

December 9, 2003 issue
61 (11_suppl_6) S19-S23

Abstract

Recently evidence has been presented that adenosine A2A and dopamine D2 receptors form functional heteromeric receptor complexes as demonstrated in human neuroblastoma cells and mouse fibroblast Ltk cells. These A2A/D2 heteromeric receptor complexes undergo coaggregation, cointernalization, and codesensitization on D2 or A2A receptor agonist treatments and especially after combined agonist treatment. It is hypothesized that the A2A/D2 receptor heteromer represents the molecular basis for the antagonistic A2A/D2 receptor interactions demonstrated at the biochemical and behavioral levels. Functional heteromeric complexes between A2A and metabotropic glutamate 5 receptors (mGluR5) have also recently been demonstrated in HEK-293 cells and rat striatal membrane preparations. The A2A/mGluR5 receptor heteromer may account for the synergism found after combined agonist treatments demonstrated in different in vitro and in vivo models. D2, A2A, and mGluR5 receptors are found together in the dendritic spines of the striatopallidal GABA neurons. Therefore, possible D2/A2A/mGluR5 multimeric receptor complexes and the receptor interactions within them may have a major role in controlling the dorsal and ventral striatopallidal GABA neurons involved in Parkinson’s disease and in schizophrenia and drug addiction, respectively.

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Information & Authors

Information

Published In

Neurology®
Volume 61Number 11_suppl_6December 9, 2003
Pages: S19-S23
PubMed: 14663004

Publication History

Published online: December 8, 2003
Published in print: December 9, 2003

Authors

Affiliations & Disclosures

K. Fuxe, MD PhD
From the Department of Neuroscience (Drs. Fuxe, Torvinen, and Terasmaa), Karolinska Institute, Stockholm, Sweden; Biomedical Sciences (Drs. Agnati, Leo, and Vergoni), University of Modena, Italy; Department of Anatomy (Dr. Staines, K. Jacobsen and B. Tinner-Staines), University of Ottawa, Canada; Stroke Branch (Dr. Hillion), NINDS, NIH, Bethesda, MD; Department of Biochemistry and Molecular Biology (Drs. Lluis, Ciruela, and Franco, M. Canals), University of Barcelona, Spain; Department of Pharmacology (Dr. Rosin), University of Virginia Health Sciences Center, Charlottesville, VA; Department of Pharmacology (Dr. Popoli), Istituto Superiore di Sanita, Rome, Italy; and Pre-clinical Pharmacology Section (Dr. Ferré), Behavioral Neuroscience Branch, NIDA, NIH, IRP, Baltimore, MD.
L.F. Agnati, MD PhD
From the Department of Neuroscience (Drs. Fuxe, Torvinen, and Terasmaa), Karolinska Institute, Stockholm, Sweden; Biomedical Sciences (Drs. Agnati, Leo, and Vergoni), University of Modena, Italy; Department of Anatomy (Dr. Staines, K. Jacobsen and B. Tinner-Staines), University of Ottawa, Canada; Stroke Branch (Dr. Hillion), NINDS, NIH, Bethesda, MD; Department of Biochemistry and Molecular Biology (Drs. Lluis, Ciruela, and Franco, M. Canals), University of Barcelona, Spain; Department of Pharmacology (Dr. Rosin), University of Virginia Health Sciences Center, Charlottesville, VA; Department of Pharmacology (Dr. Popoli), Istituto Superiore di Sanita, Rome, Italy; and Pre-clinical Pharmacology Section (Dr. Ferré), Behavioral Neuroscience Branch, NIDA, NIH, IRP, Baltimore, MD.
K. Jacobsen
From the Department of Neuroscience (Drs. Fuxe, Torvinen, and Terasmaa), Karolinska Institute, Stockholm, Sweden; Biomedical Sciences (Drs. Agnati, Leo, and Vergoni), University of Modena, Italy; Department of Anatomy (Dr. Staines, K. Jacobsen and B. Tinner-Staines), University of Ottawa, Canada; Stroke Branch (Dr. Hillion), NINDS, NIH, Bethesda, MD; Department of Biochemistry and Molecular Biology (Drs. Lluis, Ciruela, and Franco, M. Canals), University of Barcelona, Spain; Department of Pharmacology (Dr. Rosin), University of Virginia Health Sciences Center, Charlottesville, VA; Department of Pharmacology (Dr. Popoli), Istituto Superiore di Sanita, Rome, Italy; and Pre-clinical Pharmacology Section (Dr. Ferré), Behavioral Neuroscience Branch, NIDA, NIH, IRP, Baltimore, MD.
J. Hillion, PhD
From the Department of Neuroscience (Drs. Fuxe, Torvinen, and Terasmaa), Karolinska Institute, Stockholm, Sweden; Biomedical Sciences (Drs. Agnati, Leo, and Vergoni), University of Modena, Italy; Department of Anatomy (Dr. Staines, K. Jacobsen and B. Tinner-Staines), University of Ottawa, Canada; Stroke Branch (Dr. Hillion), NINDS, NIH, Bethesda, MD; Department of Biochemistry and Molecular Biology (Drs. Lluis, Ciruela, and Franco, M. Canals), University of Barcelona, Spain; Department of Pharmacology (Dr. Rosin), University of Virginia Health Sciences Center, Charlottesville, VA; Department of Pharmacology (Dr. Popoli), Istituto Superiore di Sanita, Rome, Italy; and Pre-clinical Pharmacology Section (Dr. Ferré), Behavioral Neuroscience Branch, NIDA, NIH, IRP, Baltimore, MD.
M. Canals, BSc
From the Department of Neuroscience (Drs. Fuxe, Torvinen, and Terasmaa), Karolinska Institute, Stockholm, Sweden; Biomedical Sciences (Drs. Agnati, Leo, and Vergoni), University of Modena, Italy; Department of Anatomy (Dr. Staines, K. Jacobsen and B. Tinner-Staines), University of Ottawa, Canada; Stroke Branch (Dr. Hillion), NINDS, NIH, Bethesda, MD; Department of Biochemistry and Molecular Biology (Drs. Lluis, Ciruela, and Franco, M. Canals), University of Barcelona, Spain; Department of Pharmacology (Dr. Rosin), University of Virginia Health Sciences Center, Charlottesville, VA; Department of Pharmacology (Dr. Popoli), Istituto Superiore di Sanita, Rome, Italy; and Pre-clinical Pharmacology Section (Dr. Ferré), Behavioral Neuroscience Branch, NIDA, NIH, IRP, Baltimore, MD.
M. Torvinen, PhD
From the Department of Neuroscience (Drs. Fuxe, Torvinen, and Terasmaa), Karolinska Institute, Stockholm, Sweden; Biomedical Sciences (Drs. Agnati, Leo, and Vergoni), University of Modena, Italy; Department of Anatomy (Dr. Staines, K. Jacobsen and B. Tinner-Staines), University of Ottawa, Canada; Stroke Branch (Dr. Hillion), NINDS, NIH, Bethesda, MD; Department of Biochemistry and Molecular Biology (Drs. Lluis, Ciruela, and Franco, M. Canals), University of Barcelona, Spain; Department of Pharmacology (Dr. Rosin), University of Virginia Health Sciences Center, Charlottesville, VA; Department of Pharmacology (Dr. Popoli), Istituto Superiore di Sanita, Rome, Italy; and Pre-clinical Pharmacology Section (Dr. Ferré), Behavioral Neuroscience Branch, NIDA, NIH, IRP, Baltimore, MD.
B. Tinner-Staines
From the Department of Neuroscience (Drs. Fuxe, Torvinen, and Terasmaa), Karolinska Institute, Stockholm, Sweden; Biomedical Sciences (Drs. Agnati, Leo, and Vergoni), University of Modena, Italy; Department of Anatomy (Dr. Staines, K. Jacobsen and B. Tinner-Staines), University of Ottawa, Canada; Stroke Branch (Dr. Hillion), NINDS, NIH, Bethesda, MD; Department of Biochemistry and Molecular Biology (Drs. Lluis, Ciruela, and Franco, M. Canals), University of Barcelona, Spain; Department of Pharmacology (Dr. Rosin), University of Virginia Health Sciences Center, Charlottesville, VA; Department of Pharmacology (Dr. Popoli), Istituto Superiore di Sanita, Rome, Italy; and Pre-clinical Pharmacology Section (Dr. Ferré), Behavioral Neuroscience Branch, NIDA, NIH, IRP, Baltimore, MD.
W. Staines, PhD
From the Department of Neuroscience (Drs. Fuxe, Torvinen, and Terasmaa), Karolinska Institute, Stockholm, Sweden; Biomedical Sciences (Drs. Agnati, Leo, and Vergoni), University of Modena, Italy; Department of Anatomy (Dr. Staines, K. Jacobsen and B. Tinner-Staines), University of Ottawa, Canada; Stroke Branch (Dr. Hillion), NINDS, NIH, Bethesda, MD; Department of Biochemistry and Molecular Biology (Drs. Lluis, Ciruela, and Franco, M. Canals), University of Barcelona, Spain; Department of Pharmacology (Dr. Rosin), University of Virginia Health Sciences Center, Charlottesville, VA; Department of Pharmacology (Dr. Popoli), Istituto Superiore di Sanita, Rome, Italy; and Pre-clinical Pharmacology Section (Dr. Ferré), Behavioral Neuroscience Branch, NIDA, NIH, IRP, Baltimore, MD.
D. Rosin, PhD
From the Department of Neuroscience (Drs. Fuxe, Torvinen, and Terasmaa), Karolinska Institute, Stockholm, Sweden; Biomedical Sciences (Drs. Agnati, Leo, and Vergoni), University of Modena, Italy; Department of Anatomy (Dr. Staines, K. Jacobsen and B. Tinner-Staines), University of Ottawa, Canada; Stroke Branch (Dr. Hillion), NINDS, NIH, Bethesda, MD; Department of Biochemistry and Molecular Biology (Drs. Lluis, Ciruela, and Franco, M. Canals), University of Barcelona, Spain; Department of Pharmacology (Dr. Rosin), University of Virginia Health Sciences Center, Charlottesville, VA; Department of Pharmacology (Dr. Popoli), Istituto Superiore di Sanita, Rome, Italy; and Pre-clinical Pharmacology Section (Dr. Ferré), Behavioral Neuroscience Branch, NIDA, NIH, IRP, Baltimore, MD.
A. Terasmaa, MSc
From the Department of Neuroscience (Drs. Fuxe, Torvinen, and Terasmaa), Karolinska Institute, Stockholm, Sweden; Biomedical Sciences (Drs. Agnati, Leo, and Vergoni), University of Modena, Italy; Department of Anatomy (Dr. Staines, K. Jacobsen and B. Tinner-Staines), University of Ottawa, Canada; Stroke Branch (Dr. Hillion), NINDS, NIH, Bethesda, MD; Department of Biochemistry and Molecular Biology (Drs. Lluis, Ciruela, and Franco, M. Canals), University of Barcelona, Spain; Department of Pharmacology (Dr. Rosin), University of Virginia Health Sciences Center, Charlottesville, VA; Department of Pharmacology (Dr. Popoli), Istituto Superiore di Sanita, Rome, Italy; and Pre-clinical Pharmacology Section (Dr. Ferré), Behavioral Neuroscience Branch, NIDA, NIH, IRP, Baltimore, MD.
P. Popoli, MD
From the Department of Neuroscience (Drs. Fuxe, Torvinen, and Terasmaa), Karolinska Institute, Stockholm, Sweden; Biomedical Sciences (Drs. Agnati, Leo, and Vergoni), University of Modena, Italy; Department of Anatomy (Dr. Staines, K. Jacobsen and B. Tinner-Staines), University of Ottawa, Canada; Stroke Branch (Dr. Hillion), NINDS, NIH, Bethesda, MD; Department of Biochemistry and Molecular Biology (Drs. Lluis, Ciruela, and Franco, M. Canals), University of Barcelona, Spain; Department of Pharmacology (Dr. Rosin), University of Virginia Health Sciences Center, Charlottesville, VA; Department of Pharmacology (Dr. Popoli), Istituto Superiore di Sanita, Rome, Italy; and Pre-clinical Pharmacology Section (Dr. Ferré), Behavioral Neuroscience Branch, NIDA, NIH, IRP, Baltimore, MD.
G. Leo, PhD
From the Department of Neuroscience (Drs. Fuxe, Torvinen, and Terasmaa), Karolinska Institute, Stockholm, Sweden; Biomedical Sciences (Drs. Agnati, Leo, and Vergoni), University of Modena, Italy; Department of Anatomy (Dr. Staines, K. Jacobsen and B. Tinner-Staines), University of Ottawa, Canada; Stroke Branch (Dr. Hillion), NINDS, NIH, Bethesda, MD; Department of Biochemistry and Molecular Biology (Drs. Lluis, Ciruela, and Franco, M. Canals), University of Barcelona, Spain; Department of Pharmacology (Dr. Rosin), University of Virginia Health Sciences Center, Charlottesville, VA; Department of Pharmacology (Dr. Popoli), Istituto Superiore di Sanita, Rome, Italy; and Pre-clinical Pharmacology Section (Dr. Ferré), Behavioral Neuroscience Branch, NIDA, NIH, IRP, Baltimore, MD.
V. Vergoni, PhD
From the Department of Neuroscience (Drs. Fuxe, Torvinen, and Terasmaa), Karolinska Institute, Stockholm, Sweden; Biomedical Sciences (Drs. Agnati, Leo, and Vergoni), University of Modena, Italy; Department of Anatomy (Dr. Staines, K. Jacobsen and B. Tinner-Staines), University of Ottawa, Canada; Stroke Branch (Dr. Hillion), NINDS, NIH, Bethesda, MD; Department of Biochemistry and Molecular Biology (Drs. Lluis, Ciruela, and Franco, M. Canals), University of Barcelona, Spain; Department of Pharmacology (Dr. Rosin), University of Virginia Health Sciences Center, Charlottesville, VA; Department of Pharmacology (Dr. Popoli), Istituto Superiore di Sanita, Rome, Italy; and Pre-clinical Pharmacology Section (Dr. Ferré), Behavioral Neuroscience Branch, NIDA, NIH, IRP, Baltimore, MD.
C. Lluis, PhD
From the Department of Neuroscience (Drs. Fuxe, Torvinen, and Terasmaa), Karolinska Institute, Stockholm, Sweden; Biomedical Sciences (Drs. Agnati, Leo, and Vergoni), University of Modena, Italy; Department of Anatomy (Dr. Staines, K. Jacobsen and B. Tinner-Staines), University of Ottawa, Canada; Stroke Branch (Dr. Hillion), NINDS, NIH, Bethesda, MD; Department of Biochemistry and Molecular Biology (Drs. Lluis, Ciruela, and Franco, M. Canals), University of Barcelona, Spain; Department of Pharmacology (Dr. Rosin), University of Virginia Health Sciences Center, Charlottesville, VA; Department of Pharmacology (Dr. Popoli), Istituto Superiore di Sanita, Rome, Italy; and Pre-clinical Pharmacology Section (Dr. Ferré), Behavioral Neuroscience Branch, NIDA, NIH, IRP, Baltimore, MD.
F. Ciruela, PhD
From the Department of Neuroscience (Drs. Fuxe, Torvinen, and Terasmaa), Karolinska Institute, Stockholm, Sweden; Biomedical Sciences (Drs. Agnati, Leo, and Vergoni), University of Modena, Italy; Department of Anatomy (Dr. Staines, K. Jacobsen and B. Tinner-Staines), University of Ottawa, Canada; Stroke Branch (Dr. Hillion), NINDS, NIH, Bethesda, MD; Department of Biochemistry and Molecular Biology (Drs. Lluis, Ciruela, and Franco, M. Canals), University of Barcelona, Spain; Department of Pharmacology (Dr. Rosin), University of Virginia Health Sciences Center, Charlottesville, VA; Department of Pharmacology (Dr. Popoli), Istituto Superiore di Sanita, Rome, Italy; and Pre-clinical Pharmacology Section (Dr. Ferré), Behavioral Neuroscience Branch, NIDA, NIH, IRP, Baltimore, MD.
R. Franco, PhD
From the Department of Neuroscience (Drs. Fuxe, Torvinen, and Terasmaa), Karolinska Institute, Stockholm, Sweden; Biomedical Sciences (Drs. Agnati, Leo, and Vergoni), University of Modena, Italy; Department of Anatomy (Dr. Staines, K. Jacobsen and B. Tinner-Staines), University of Ottawa, Canada; Stroke Branch (Dr. Hillion), NINDS, NIH, Bethesda, MD; Department of Biochemistry and Molecular Biology (Drs. Lluis, Ciruela, and Franco, M. Canals), University of Barcelona, Spain; Department of Pharmacology (Dr. Rosin), University of Virginia Health Sciences Center, Charlottesville, VA; Department of Pharmacology (Dr. Popoli), Istituto Superiore di Sanita, Rome, Italy; and Pre-clinical Pharmacology Section (Dr. Ferré), Behavioral Neuroscience Branch, NIDA, NIH, IRP, Baltimore, MD.
S. Ferré, MD PhD
From the Department of Neuroscience (Drs. Fuxe, Torvinen, and Terasmaa), Karolinska Institute, Stockholm, Sweden; Biomedical Sciences (Drs. Agnati, Leo, and Vergoni), University of Modena, Italy; Department of Anatomy (Dr. Staines, K. Jacobsen and B. Tinner-Staines), University of Ottawa, Canada; Stroke Branch (Dr. Hillion), NINDS, NIH, Bethesda, MD; Department of Biochemistry and Molecular Biology (Drs. Lluis, Ciruela, and Franco, M. Canals), University of Barcelona, Spain; Department of Pharmacology (Dr. Rosin), University of Virginia Health Sciences Center, Charlottesville, VA; Department of Pharmacology (Dr. Popoli), Istituto Superiore di Sanita, Rome, Italy; and Pre-clinical Pharmacology Section (Dr. Ferré), Behavioral Neuroscience Branch, NIDA, NIH, IRP, Baltimore, MD.

Notes

Address correspondence and reprint requests to Dr. Kjell Fuxe, Department of Neuroscience, Karolinska Institutet, Retzius väg 8, A2:4, S17177, Stockholm, Sweden; e-mail: [email protected]

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