Duramycin enhances chloride secretion in airway epithelium.
The effect of duramycin, a polypeptide antibiotic, on Cl- transport in canine tracheal epithelium mounted in Ussing chambers was studied. Over a narrow concentration range, duramycin increased short-circuit current (Isc) and net Cl- secretion and had no effect on mannitol flux when added to the mucosal bathing solution. The maximum increase in Isc was observed at a duramycin concentration of 2 X 10(-6) M and was associated with an increase in both unidirectional Cl- fluxes. Higher duramycin concentrations produced a decrease in Isc. Submucosal addition of duramycin had no effect on Isc except at high concentrations. Pretreatment of tissues with mucosal amiloride (10(-4) M) to reduce basal Na+ transport had no effect on the subsequent response to duamycin. In other tissues pretreated with 10(-3) M dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP), duramycin produced a further increase in Isc and net Cl- secretion similar to its effect in nonpretreated tissues. In all instances the increase in Isc was entirely accounted for by an increase in net Cl- secretion. We conclude that duramycin increases Isc and Cl- secretion in airway epithelium. Although the mechanism of activation is not known, these data demonstrate that duramycin increases Cl- secretion by a pathway other than cAMP. An understanding of the mechanism of action of duramycin may further our understanding of Cl- secretion regulation in airway epithelium.
Cloutier
M M
MM
Department of Pediatrics, University of Connecticut Health Center, Farmington 06032.
Guernsey
L
L
Mattes
P
P
Koeppen
B
B
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001430:Bacteriocins; D002712:Chlorides / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology; D004285:Dogs; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009092:Mucous Membrane / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D014132:Trachea / Q000502:physiology*
D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D002712:Chlorides; D010455:Peptides; C040522:duramycin; D000242:Cyclic AMP