Examination of luminal acetylcholine on CFTR activity in porcine airway epithelium

Abstract

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 (ISC) 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 ISC. This ACh effect was not changed by amiloride. In the presence of amiloride the IBMX/forskolin‐activated current (ΔII/F) was 32.4±6.4 μA/cm2 (n=6). GlyH‐101 reduced ΔII/F to 13.1±3.7 μA/cm2 (n=6) demonstrating that a substantial portion of that current is CFTR dependent. However, GlyH‐101 did not altered the effect of luminal ACh (ΔIACh: 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.