Regulation of ion transport across porcine distal bronchi

Distal airways comprise the vast majority of total human airway surface area, yet little is known about transepithelial ion transport in these tissues. Pathways that regulate ion transport in porcine small bronchi (3.62 +/- 0.04 mm outer diameter) were studied by measuring the effects of secretogogues that stimulate Cl- secretion in proximal airways. Resting potential difference (PD), shortcircuit current (ISC), and resistance (Rt) across the distal bronchi were 3.4 +/- 0.1 mV (lumen negative), 40.8 +/- 1.7 microA/cm2, and 92.1 +/- 5.0 omega.cm2, respectively. Isoproterenol (10 microM), acetylcholine (ACh; 10 microM), or ATP (100 microM) induced immediate significant (P < 0.05) increases in PD and ISC. The Ca2+ ionophore A23187 (1 microM) induced a slow increase in PD that was accompanied by a significant 2.4-fold increase in Rt and no change in ISC. The responses to isoproterenol, ACh, and ATP were maintained in the presence of 10 microM amiloride. Pretreatment with 10 microM bumetanide to block Cl- secretion inhibited responses to isoproterenol and ATP but not to ACh. The ACh effect was inhibited only after both Cl- and HCO3- secretion were blocked. These data suggest that isoproterenol, ACh, and ATP stimulate anion secretion. Isoproterenol and ATP specifically stimulate Cl- secretion, whereas ACh can stimulate both Cl- and HCO3- secretion. A23187 has no effect on active transepithelial ion transport but increases barrier resistance in intact distal bronchial epithelium.