Insulin and insulin‐like growth factor type‐I up‐regulate the vanilloid receptor‐1 (TRPV1) in stably TRPV1‐expressing SH‐SY5Y neuroblastoma cells

Abstract

The capsaicin receptor, transient receptor potential, vanilloid type 1 (TRPV1), is a Ca²⁺‐permeable ion channel activated by noxious stimuli eliciting pain. Several reports have shown modulation of TRPV1 activity and expression by neuronal growth factors. Here, we study the long‐term effects on TRPV1 expression mediated by insulin‐like growth factor type‐I (IGF‐I) and insulin in a stably TRPV1‐expressing SH‐SY5Y neuroblastoma cell line. We show that, after 72 hr of 10 nM IGF‐I or insulin exposure, the TRPV1 protein level was up‐regulated 2.5‐ and 2‐fold, respectively. By blocking phosphatidylinositol‐3‐kinase [PI(3)K] or mitogen‐activated protein kinase (MAPK) signaling, we concluded that the increase in total TRPV1 protein content induced by IGF‐I was controlled by PI(3)K signaling, whereas insulin seemed to regulate TRPV1 protein expression via both PI(3)K and MAPK pathways. Inhibiting protein kinase C (PKC) blocked the effects of both IGF‐I and insulin. Furthermore, the concentrations causing a 50% Ca²⁺ increase (EC₅₀) after insulin and IGF‐I treatments were significantly lowered compared with untreated cells. We conclude that IGF‐I and insulin enhance TRPV1 protein expression and activity, and impaired pain sensation might result from distorted TRPV1 regulation in the peripheral nervous system.