scholarly journals Allosteric Interactions between Adenosine A2A and Dopamine D2 Receptors in Heteromeric Complexes: Biochemical and Pharmacological Characteristics, and Opportunities for PET Imaging

2021 ◽  
Vol 22 (4) ◽  
pp. 1719
Author(s):  
Kavya Prasad ◽  
Erik F. J. de Vries ◽  
Philip H. Elsinga ◽  
Rudi A. J. O. Dierckx ◽  
Aren van Waarde

Adenosine and dopamine interact antagonistically in living mammals. These interactions are mediated via adenosine A2A and dopamine D2 receptors (R). Stimulation of A2AR inhibits and blockade of A2AR enhances D2R-mediated locomotor activation and goal-directed behavior in rodents. In striatal membrane preparations, adenosine decreases both the affinity and the signal transduction of D2R via its interaction with A2AR. Reciprocal A2AR/D2R interactions occur mainly in striatopallidal GABAergic medium spiny neurons (MSNs) of the indirect pathway that are involved in motor control, and in striatal astrocytes. In the nucleus accumbens, they also take place in MSNs involved in reward-related behavior. A2AR and D2R co-aggregate, co-internalize, and co-desensitize. They are at very close distance in biomembranes and form heteromers. Antagonistic interactions between adenosine and dopamine are (at least partially) caused by allosteric receptor–receptor interactions within A2AR/D2R heteromeric complexes. Such interactions may be exploited in novel strategies for the treatment of Parkinson’s disease, schizophrenia, substance abuse, and perhaps also attention deficit-hyperactivity disorder. Little is known about shifting A2AR/D2R heteromer/homodimer equilibria in the brain. Positron emission tomography with suitable ligands may provide in vivo information about receptor crosstalk in the living organism. Some experimental approaches, and strategies for the design of novel imaging agents (e.g., heterobivalent ligands) are proposed in this review.

Neuroreport ◽  
2000 ◽  
Vol 11 (4) ◽  
pp. 743-748 ◽  
Author(s):  
Osamu Ogawa ◽  
Hiroyuki Umegaki ◽  
Kiichi Ishiwata ◽  
Yukako Asai ◽  
Hiroyuki Ikari ◽  
...  

Synapse ◽  
2002 ◽  
Vol 43 (3) ◽  
pp. 195-200 ◽  
Author(s):  
Hiroyuki Umegaki ◽  
Kiichi Ishiwata ◽  
Osamu Ogawa ◽  
Donald K. Ingram ◽  
George S. Roth ◽  
...  

Neuroscience ◽  
2010 ◽  
Vol 166 (4) ◽  
pp. 1056-1067 ◽  
Author(s):  
A.M. Farrar ◽  
K.N. Segovia ◽  
P.A. Randall ◽  
E.J. Nunes ◽  
L.E. Collins ◽  
...  

1990 ◽  
Vol 183 (4) ◽  
pp. 1414
Author(s):  
N.P.L.G. Verhoeff ◽  
M. Bobeldijk ◽  
E.A. van Royen ◽  
M.G.P. Feenstra ◽  
G.J. Boer ◽  
...  

2000 ◽  
Vol 166 (2) ◽  
pp. 287-297 ◽  
Author(s):  
Dalia M. Araujo ◽  
Simon R. Cherry ◽  
Keith J. Tatsukawa ◽  
Tatsushi Toyokuni ◽  
Harley I. Kornblum

2003 ◽  
Vol 306 (2) ◽  
pp. 544-549 ◽  
Author(s):  
Toshio Kamiya ◽  
Osamu Saitoh ◽  
Kazuaki Yoshioka ◽  
Hiroyasu Nakata

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