Mechanosensory Signaling in Enterochromaffin Cells and 5-HT Release: Potential Implications for Gut Inflammation.

摘要: Enterochromaffin cells (EC) synthesize 95% of the body 5-HT and release in response to mechanical or chemical stimulation. EC cell has physiological effects on gut motility, secretion visceral sensation. Abnormal regulation occurs gastrointestinal disorders Inflammatory Bowel Diseases (IBD) where may represent a key player pathogenesis intestinal inflammation. The focus this review is mechanism(s) involved ‘mechanosensation’ critical gaps our knowledge for future research. Much concepts are from human BON model EC, although more recent work included other lines, native mouse intact mucosa. ‘mechanosensors’ that respond physical forces generated during peristaltic activity by translating stimulus (MS) into an intracellular biochemical leading ATP release. emerging picture mechanosensation includes Piezo 2 channels, caveolin-rich microdomains tight purines. ‘purinergic hypothesis’ MS releases purines act autocrine / paracrine manner activate excitatory (P2Y1, P2Y4, P2Y6, A2A/A2B) inhibitory (P2Y12, A1, A3) receptors regulate activates P2Y1/Gαq/PLC/IP3-IP3R/SERCA Ca2+signaling pathway, A2A/A2B–Gs/AC/cAMP-PKA signaling ATP-gated P2X3 channel, P2Y12 -Gi/o/AC-cAMP pathway. In IBD, down regulated A2B up cells, but pathophysiological consequences abnormal mechanosensory purinergic remain unknown. remains poorly understood.