Trans-activation of TRPV1 by D1R in mouse dorsal root ganglion neurons

Abstract

TRPV1, a ligand-gated ion channel expressed in nociceptive sensory neurons is modulated by a variety of intracellular signaling pathways. Dopamine is a neurotransmitter that plays important roles in motor control, cognition, and pain modulation in the CNS, and acts via a variety of dopamine receptors (D1R-D5R), a class of GPCRs. Although nociceptive sensory neurons express D1-like receptors, very little is known about the effect of dopamine on TRPV1 in the peripheral nervous system. Therefore, in this study, we examined the effects of D1R activation on TRPV1 in mouse DRG neurons using Ca2+ imaging and immunohistochemical analysis. The D1R agonist SKF-38393 induced reproducible Ca2+ responses via Ca2+ influx through TRPV1 rather than Ca2+ mobilization from intracellular Ca2+ stores. Immunohistochemical analysis revealed co-expression of D1R and TRPV1 in mouse DRG neurons. The PLC-specific inhibitor blocked the SKF-38393-induced Ca2+ response, whereas the PKC, DAG lipase, AC, and PICA inhibitors had no effect on the SKF-38393-induced Ca2+ response. Taken together, our results suggest that the SKF-38393-induced Ca2+ response results from the direct activation of TRPV1 by a PLC/DAG-mediated membrane-delimited pathway. These results provide evidence that the trans-activation of TRPV1 following D1R activation may contribute to the modulation of pain signaling in nociceptive sensory neurons.