Insulin and insulin-like growth factor type-I up-regulate the vanilloid receptor-1 (TRPV1) in stably TRPV1-expressing SH-SY5Y neuroblastoma cells.
The capsaicin receptor, transient receptor potential, vanilloid type 1 (TRPV1), is a Ca(2+)-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% Ca(2+) increase (EC(50)) 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.
Lilja
Johanna
J
Department of Neurochemistry, Stockholm University, Stockholm, Sweden. johanna@neurochem.su.se
Laulund
Frida
F
Forsby
Anna
A
D000704:Analysis of Variance; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D050916:TRPV Cation Channels / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation
D007328:Insulin; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium