TRPV4 regulated cAMP-dependent neurite growth.
A, treatment of PC12 cells with 1 mm cAMP increased the transcript levels of PLA2 and TRPV4, but co-treatment with PD098059 inhibited these transcript level increases. B, treatment of 1 mm cAMP increased the protein expression of PLA2 and TRPV4. C and D, PC12 cells treated with 1 mm cAMP showed markedly enhanced neurite growth, and co-treatment with 250 nm melittin augmented this growth, whereas co-treatment with 10 μm PD098095 or 20 μm AACOCF3 suppressed cAMP-induced neurite growth (C). The TRPV4 activators, AA, 5,6-EET, and 4α-PDD augmented cAMP-induced neurite growth (D). ***, p < 0.001 versus untreated cells (CTL); ###, p < 0.001 versus cAMP-treated cells (cAMP). E and F, treatment of PC12 cells with 10 μm forskolin (FSK) significantly promoted neurite growth, and co-treatment with melittin augmented this growth, but co-treatment with PD098095 or AACOCF3 suppressed FSK-induced neurite growth (E). The TRPV4 activators, AA, 5,6-EET, and 4α-PDD augmented cAMP-induced neurite growth (F).