Serotonin and histamine sensitise TRPV4 response to 4alphaPDD both in vivo (increased visceral hypersensitivity) and in vitro, in sensory neurons, by a PKC, PLA(2), PLCbeta and MAPKK-dependent mechanism. Serotonin and histamine caused a MAPKK-dependent increase in TRPV4 expression in colonic sensory neurons plasma membranes. Further, histamine- or serotonin-mediated visceral hypersensitivity depend on TRPV4 expression in sensory neurons. TRPV4 appears as a common mechanism to several known mediators of visceral hypersensitivity.
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