Adenosine A1-Dopamine D1 Receptor Heteromers Control the Excitability of the Spinal Motoneuron

Autor: Vicent Casadó, Sergi Ferré, Yocasta Álvarez-Bagnarol, Marla Rivera-Oliver, Nicole Cruz-Reyes, Christian Ayala-Santiago, Manuel Díaz-Ríos, Stefan Clemens, Estefanía Moreno, Enric I. Canela, Gian Carlo Molina-Castro
Rok vydání: 2018
Předmět:
Zdroj: Molecular Neurobiology. 56:797-811
ISSN: 1559-1182
0893-7648
DOI: 10.1007/s12035-018-1120-y
Popis: While the role of the ascending dopaminergic system in brain function and dysfunction has been a subject of extensive research, the role of the descending dopaminergic system in spinal cord function and dysfunction is just beginning to be understood. Adenosine plays a key role in the inhibitory control of the ascending dopaminergic system, largely dependent on functional complexes of specific subtypes of adenosine and dopamine receptors. Combining a selective destabilizing peptide strategy with a proximity ligation assay and patch-clamp electrophysiology in slices from male mouse lumbar spinal cord, the present study demonstrates the existence of adenosine A1-dopamine D1 receptor heteromers in the spinal motoneuron by which adenosine tonically inhibits D1 receptor-mediated signaling. A1-D1 receptor heteromers play a significant control of the motoneuron excitability, represent main targets for the excitatory effects of caffeine in the spinal cord and can constitute new targets for the pharmacological therapy after spinal cord injury, motor aging-associated disorders and restless legs syndrome.
Databáze: OpenAIRE
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