Activation of TRPV4 triggers ATP release and mast cell dependent contraction of airway smooth muscle (ASM)

The emerging role of transient receptor potential channels in chronic lung disease

“…A wide range of proinflammatory, disease-relevant stimuli are known to activate TRPV4, so it is not surprising that activation may give rise to functional effects that could play a role in the pathophysiology of chronic lung diseases. For example, it has been demonstrated that TRPV4 agonists can evoke bronchospasm in an in vivo anaesthetised guinea pig model, although in this case sensory nerve reflexes are not involved since both vagus nerves were cut [134]. Consistent with this are observations that a TRPV4 agonist can evoke a mast-cell dependent contractile response of human bronchi and guinea pig tracheal airway smooth muscle in vitro.…”

“…This effect is thought to be mediated by TRPV4-mediated ATP release from airway smooth muscle, which activates P2X4 receptors on mast cells to release cysteinyl leukotrienes (LT) which activate the Cys LT 1 receptor to evoke contraction [112,134]. Interestingly, many of the functional effects of TRPV4 activation are due to the release of ATP and activation of purinoceptors [8,82,99,134,135] and TRPV4-induced ATP release has been demonstrated in human macrophages, epithelial and smooth muscle cells [99,113,135]. In addition, TRPV4-induced ATP release has been shown to be released via a pannexin 1-dependent mechanism [82,99,135].…”