Transient receptor potential vanilloid-1 (TRPV1) is a ligand-gated ion channel expressed on nociceptive sensory neuron, which transduces extracellular stimuli such as noxious heat, proton, and capsaicin. It is well known the activity of TRPV1 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 central nervous system (CNS). Dopamine receptor is a class of G-protein coupled receptor (GPCR) that regulates cellular functions through its downstream intracellular signaling pathways. Previous studies have demonstrated the expression of D1-like receptors (D1R and D5R) in nociceptive sensory neurons. However, the effect of dopamine receptor on TRPV1 remains unknown.This study was designated to examine the effects of D1R activation on TRPV1 in mouse dorsal root ganglion (DRG) neuron using Ca2+ imaging and immunofluorescence. It was found that D1R agonist SKF-38393 induces reproducible Ca2+ response in nociceptive sensory neurons. The SKF-38393-induced Ca2+ response results from influx through TRPV1 rather than Ca2+ mobilization from intracellular Ca2+ stores. Immunofluorescence analysis revealed co-expression of D1R and TRPV1 in DRG neurons. Whereas PKC inhibitor, diacylglycerol (DAG) lipase inhibitor, adenylyl cyclase (AC) inhibitor, and PKA inhibitor had no effects on SKF-38393-induced Ca2+ response, phospholipase C (PLC) specific inhibitor blocked SKF-38393-induced Ca2+ response, Taken together, these data suggest that Ca2+ response by SKF-38393 result from direct activation of TRPV1 by PLC/DAG-mediated membrane-delimited pathway.In conclusion, these results provide strong evidence that trans-activation of TRPV1 following D1R activation may contribute to the modulation of pain signaling in nociceptive sensory neurons.
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Activation of TRPV1 by D1R agonist SKF-38393 in mouse dorsal root ganglion neuron
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