Examination of luminal acetylcholine on CFTR activity in porcine airway epithelium

The CFTR plays a crucial role in airway fluid homeostasis since mutations are associated with cystic fibrosis lung disease. Luminal acetylcholine (ACh) has been identified to activate Cl − secretion in airway epithelia although the underlying mechanisms and targets are not identified. The present study investigates whether or not the CFTR is a putative target of luminal ACh. Porcine tracheal preparations were mounted in Ussing‐chambers for short‐circuit‐current (I SC ) recordings. ACh (100 μM) was applied from the luminal side. CFTR‐dependent Cl − secretion was assessed by application of IBMX/forskolin (100/10 μM, luminal) in the presence of amiloride (10 μM, luminal). GlyH‐101 (50 μM, luminal) was used to block CFTR currents. Application of luminal ACh significantly increased I SC . This ACh effect was not changed by amiloride. In the presence of amiloride the IBMX/forskolin‐activated current (ΔI I/F ) was 32.4±6.4 μA/cm 2 (n=6). GlyH‐101 reduced ΔI I/F to 13.1±3.7 μA/cm 2 (n=6) demonstrating that a substantial portion of that current is CFTR dependent. However, GlyH‐101 did not altered the effect of luminal ACh (ΔI ACh : 11.3±2.3 (control); 10.1±2.2 (GlyH‐101); n=5). From these results it can be concluded that luminal ACh activates ion transport processes in porcine airway epithelium. Nevertheless this neither includes CFTR‐dependent Cl − secretion nor ENaC‐dependent Na + reabsorption.