[HTML][HTML] Complex formation and functional interaction between adenosine A1 receptor and type-1 metabotropic glutamate receptor

Y Kamikubo, T Tabata, H Sakairi, Y Hashimoto… - Journal of …, 2015 - Elsevier
Y Kamikubo, T Tabata, H Sakairi, Y Hashimoto, T Sakurai
Journal of Pharmacological Sciences, 2015Elsevier
The adenosine A1 receptor (A1R) is a G protein-coupled receptor (GPCR) for adenosine, a
ubiquitous neuromodulator, and thus regulates neuronal excitability, as well as arousal and
sensitivity to pain. In addition, we have previously described a new mode of action for A1R:
in cerebellar Purkinje cells, its activation attenuates neuronal responses to glutamate, as
mediated by the type-1 metabotropic glutamate receptor (mGluR1). mGluR1 is also a GPCR,
and elicits such responses as long-term depression of the postsynaptic response to …
Abstract
The adenosine A1 receptor (A1R) is a G protein-coupled receptor (GPCR) for adenosine, a ubiquitous neuromodulator, and thus regulates neuronal excitability, as well as arousal and sensitivity to pain. In addition, we have previously described a new mode of action for A1R: in cerebellar Purkinje cells, its activation attenuates neuronal responses to glutamate, as mediated by the type-1 metabotropic glutamate receptor (mGluR1). mGluR1 is also a GPCR, and elicits such responses as long-term depression of the postsynaptic response to glutamate, a cellular basis for cerebellar motor learning. Here, we explore in greater detail the interaction between A1R and mGluR1 using non-neuronal cells. Co-immunoprecipitation and Förster resonance energy transfer (FRET) analysis reveal that A1R and mGluR1 form a complex. Furthermore, we found that mGluR1 activation inhibits A1R signaling, as measured by changes in intracellular cAMP. These findings demonstrate that A1R and mGluR1 have the intrinsic ability to form a heteromeric complex and mutually modulate signaling. This interaction may represent a new form of intriguing GPCR-mediated cellular responses.
Elsevier