Adenosine A 1-Dopamine D 1 Receptor Heteromers Control the Excitability of the Spinal Motoneuron

Mol Neurobiol. 2019 Feb;56(2):797-811. doi: 10.1007/s12035-018-1120-y. Epub 2018 May 24.

Abstract

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.

Keywords: Adenosine A1 receptor; Dopamine D1 receptor; Motoneuron; Receptor heteromers; Spinal cord.

MeSH terms

  • Adenosine / pharmacology
  • Caffeine / pharmacology*
  • Cells, Cultured
  • Dopamine / pharmacology
  • Humans
  • Motor Neurons / drug effects*
  • Neurons, Efferent / drug effects
  • Receptors, Dopamine D1 / drug effects*
  • Spinal Cord / drug effects*
  • Synaptic Transmission / drug effects

Substances

  • Receptors, Dopamine D1
  • Caffeine
  • Adenosine
  • Dopamine