Metabotropic glutamate 1alpha and adenosine A1 receptors assemble into functionally interacting complexes.
Recently, evidence has emerged that seven transmembrane G protein-coupled receptors may be present as homo- and heteromers in the plasma membrane. Here we describe a new molecular and functional interaction between two functionally unrelated types of G protein-coupled receptors, namely the metabotropic glutamate type 1alpha (mGlu(1alpha) receptor) and the adenosine A1 receptors in cerebellum, primary cortical neurons, and heterologous transfected cells. Co-immunoprecipitation experiments showed a close and subtype-specific interaction between mGlu(1alpha) and A1 receptors in both rat cerebellar synaptosomes and co-transfected HEK-293 cells. By using transiently transfected HEK-293 cells a synergy between mGlu(1alpha) and A1 receptors in receptor-evoked [Ca(2+)](i) signaling has been shown. In primary cultures of cortical neurons we observed a high degree of co-localization of the two receptors, and excitotoxicity experiments in these cultures also indicate that mGlu(1alpha) and A1 receptors are functionally related. Our results provide a molecular basis for adenosine/glutamate receptors cross-talk and open new perspectives for the development of novel agents to treat neuropsychiatric disorders in which abnormal glutamatergic neurotransmission is involved.
Ciruela
F
F
Department of Biochemistry, University of Barcelona, 08028 Barcelona, Spain.
Escriche
M
M
Burgueno
J
J
Angulo
E
E
Casado
V
V
Soloviev
M M
MM
Canela
E I
EI
Mallol
J
J
Chan
W Y
WY
Lluis
C
C
McIlhinney
R A
RA
Franco
R
R
D000818:Animals; D002460:Cell Line; D002531:Cerebellum / Q000378:metabolism; D006801:Humans; D051381:Rats; D020239:Receptor Cross-Talk; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D015398:Signal Transduction; D013574:Synaptosomes / Q000378:metabolism
D018094:Receptors, Metabotropic Glutamate; D018047:Receptors, Purinergic P1; C104077:metabotropic glutamate receptor type 1