Water Channel (Aquaporin 3) Gene Activation Correlates with Substance P in ARDS

摘要

Substance P (SP) is an important member of tachykinin and consists of 11 amino-acids: Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2. In the human respiratory tract, SP is synthesized in the ribosome of the primary sensory neurons and neurons intrinsic plexus as a larger protein and then enzymatically converted into the active undecapeptide. SP-immunoreactive nerves are located beneath and within the epithelium, around submucosal bronchial glands, bronchial blood vessels, and to a lesser extent within airway smooth muscle. The effects of SP on target cells are mediated by at least three specific receptors, the neurokinin-1 receptor (NK-1R), NK-2R, and NK-3R. But SP appears to preferentially activate a distinct NK-1R (the relative affinity is 100 and 500-fold higher than for NK-2R and NK-3R, respectively). Although SP is known to be involved in 'neurogenic inflammation' that links to normal physiology and pulmonary diseases such as acute lung injury, its signal transduction pathways in many pathophysiological processes remains unclear. In this regard, we examined transcriptome alterations in the homolized lung tissue in a rat model of smoke inhalation injury. We found that a specific NK-1R antagonist significantly attenuated a water channel (aquaporin 3) gene expression. Our finding revealed that SP, via its NK-1R, could have clinical utilization in a water balance-related pathophysiological process through modulation of water channels.