Dominant role of interstitial cells of Cajal in nitrergic relaxation of murine lower oesophageal sphincter

摘要: Oesophageal achalasia is a disease known to result from reduced relaxation of the lower oesophageal sphincter (LES). Nitric oxide (NO) one main inhibitory transmitters. NO-sensitive guanylyl cyclase (NO-GC) acts as key target NO and, by generation cGMP, mediates nitrergic in LES. To date, exact mechanism LES still insufficiently elucidated. clarify role NO-GC relaxation, we used cell-specific knockout (KO) mouse lines for NO-GC. These include mice lacking smooth muscle cells (SMC-GCKO), interstitial Cajal (ICC-GCKO) and both SMC/ICC (SMC/ICC-GCKO). We applied manometry study functionality vivo. Isometric force studies were performed monitor responsiveness exogenous electric field stimulation intrinsic nerves vitro. Cell-specific expression/deletion was monitored immunohistochemistry. Swallowing-induced strongly deletion ICC. Basal tone affected either SMC or Lack leads complete interruption NO-induced therefore, an achalasia-like phenotype similar that seen global GCKO mice. Our data indicate regulation basal based on dual mediated ICC whereas swallow-induced mainly regulated mechanisms