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J Appl Physiol 93: 873-881, 2002. First published May 3, 2002; doi:10.1152/japplphysiol.00174.2002
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Vol. 93, Issue 3, 873-881, September 2002

Effects of ion transport inhibitors on MCh-mediated secretion from porcine airway submucosal glands

Jonathan E. Phillips, John A. Hey, and Michel R. Corboz

Allergy, Schering-Plough Research Institute, Kenilworth, New Jersey 07033

Submucosal glands secrete macromolecules and liquid that are essential for normal airway function. To determine the mechanisms responsible for airway gland secretion and the interaction between gland secretion and epithelial ion transport, studies were performed in porcine tracheal epithelia by using the hillocks and Ussing techniques. No significant baseline gland fluid flux (JG) was measured by the hillocks technique after 3 min, and the epithelia had an average potential difference of 7.5 ± 0.5 mV (lumen negative) with a short-circuit current of 73 ± 4 µA/cm2, as measured by the Ussing technique. The secretagogue methacholine induced concentration-dependent increases in JG after 3 min from 0.003 µl · min-1 · cm-2 at 0.1 µM to 0.41 ± 0.04 µl · min-1 · cm-2 at 1,000 µM, with a 0.9 ± 0.1 mV hyperpolarization of the epithelium at 1,000 µM. When the epithelium was pretreated for 3 min with the sodium channel blocker amiloride, the methacholine (1,000 µM)-induced JG increased to 0.67 ± 0.09 µl · min-1 · cm-2, and the hyperpolarization increased to 2.2 ± 0.5 mV over the amiloride-pretreated level. When pretreated for 3 min with the chloride channel blocker diphenylamine-2-carboxylic acid, the methacholine (1,000 µM)-induced JG was inhibited to 0.20 ± 0.06 µl · min-1 · cm-2, and the methacholine-induced hyperpolarization was abolished. These data indicate that, in porcine airways, methacholine-induced JG may be increased by inhibition of sodium absorption and decreased by inhibition of chloride secretion.

mucus; hillock; amiloride; diphenylamine-2-carboxylic acid; Ussing; 5-nitro-2-(3-phenylpropylamino)benzoic acid


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