p-Aminohippurate transport in canine tracheal epithelium.

The unidirectional fluxes of 20, 100, 500, and 2,000 microM rho-aminohippurate (PAH) were measured under open- and short-circuit conditions in canine tracheal epithelium mounted as flat sheets in Ussing chambers. In tissues pretreated with mucosal indomethacin (10(-6) M) and amiloride (10(-4) M), unidirectional PAH fluxes under short-circuit conditions increased with increasing bath concentrations but there was no significant net PAH transport. After stimulation of chloride secretion by mucosal cyclic adenosine 3',5' -cyclic monophosphate (cAMP 10(-3) M), there was a significant increase in the secretory flux of PAH and a significant decrease in the absorptive flux of PAH. This resulted in net PAH secretion that demonstrated saturation kinetics with an apparent Michaelis-Menten constant of 754 microM by Lineweaver-Burk analysis. Intracellular concentrations of PAH were 0.4-1.2 times bath concentrations after pretreatment with indomethacin and amiloride and increased to 2.6-3.3 times bath concentrations after cAMP. Under open-circuit conditions, secretory PAH flux decreased and absorptive flux increased resulting in net PAH absorption. We conclude from these early studies that the canine tracheal epithelium possesses a specialized system for the transport of organic anions in the airways and that this transport system may share many similarities with organic anion transport in the kidney.

Effects of cAMP, furosemide, and ouabain on transtracheal tetracycline and chloramphenicol influx in the rat.

Using an in vitro perfusion model of the rat trachea, we studied the effects of dibutyryl cAMP (10(-3)M), terbutaline sulfate (1.7 X 10(-4)M), furosemide (10(-3)M), and ouabain (10(-3)M) on net transtracheal tetracycline and chloramphenicol influx. Submucosal cAMP and terbutaline increased transepithelial potential difference and short-circuit current and net tetracycline influx from control values of 0.496 +/- 0.066 (mean +/- SEM, n = 9) and 0.451 +/- 0.077 nM/cm2 h (n = 7) by 51 and 29%, respectively. Submucosal furosemide and ouabain decreased transepithelial potential difference, short-circuit current, and net tetracycline influx from control values by 22 and 29%, respectively. Neither cAMP, terbutaline, furosemide, nor ouabain had any effect on net chloramphenicol influx. These data suggest that drugs used in conjunction with antibiotics in patients with obstructive pulmonary disease may alter delivery of certain antibiotics into the airway lumen.

Effect of cotton bracts extract on canine tracheal epithelium and shunt pathway.

The effects of increasing concentrations (5 to 100 microliters) of an aqueous extract of cotton bracts (CBE) on the electrophysiologic properties and paracellular pathway of the canine trachea mounted in Ussing chambers were examined. The CBE produced a 50% decrease in short-circuit current and a dose-dependent decrease in transepithelial potential difference and tissue resistance when added to the mucosal bathing solution. The decrease in tissue resistance after exposure to 25 and 100 microliters was followed by an increase in mannitol flux, suggesting an effect on the paracellular pathway. No significant effect on mannitol flux was seen after 5 microliters CBE, when results were compared with control tissues from the same dog. The effects of 5 microliters CBE but not higher concentrations were reversible. Submucosal CBE had no effect on the electrophysiologic properties of the canine trachea or on mannitol flux. We conclude that in the canine tracheal epithelium, CBE inhibits active ion transport, alters the paracellular pathway, and acts only from the luminal surface.