Suppressive effect of transient receptor potential vanilloid 1 on olfactory receptor signal transduction

We investigated the effect of transient receptor potential vanilloid 1 (TRPV1) on ligand-stimulated olfactory receptor (OR) activation [intracellular cyclic adenosine monophosphate (cAMP) elevation]. The co-expression of TRPV1 with OR51E1 in HEK293T cells suppressed the activation of OR51E1 stimulated with isovaleric acid. This suppression was further potentiated by capsaicin stimulation. On the other hand, capsaicin suppressed the ligand-induced cAMP production in HEK293T cells expressing OR51E1 without co-transfection of the TRPV1 expression plasmid. Treatment with siRNA for TRPV1 offset this capsaicin's effect on ligand-induced OR51E1 activation, suggesting the involvement of endogenously expressed TRPV1 in this suppression. Additionally, TRPV1-dependent suppression of OR51E1 activation was abolished by Ca2+ depletion in the extracellular fluid. A calcium ionophore (A23187) exhibited effects like TRPV1 on the OR response. Furthermore, the suppressive effect of A23187 was inhibited by a G protein-coupled receptor kinase (GRK) inhibitor, CCG21022. Our results indicate that TRPV1 suppresses OR activation via Ca²⁺ influx, followed by GRK activation.