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J Appl Physiol (May 3, 2002). doi:10.1152/japplphysiol.00174.2002
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Articles in PresS, published online ahead of print May 3, 2002
J Appl Physiol, 10.1152/jap.00174.2002
Submitted on March 4, 2002
Accepted on April 26, 2002

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

Jonathan E Phillips1*, John A Hey1, and Michel R Corboz1

1 Allergy, Schering-Plough Research Institute, Kenilworth, NJ, USA

* To whom correspondence should be addressed. E-mail: jonathan.phillips{at}spcorp.com.

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 using the hillocks and Ussing techniques. No significant baseline gland fluid flux (JG) was measured by the hillocks technique after three minutes 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 three minutes from 0.003 µl/min/cm2 at 0.1 µM to 0.41±0.04 µl/min/cm2 at 1000 µM, with a 0.9±0.1 mV hyperpolarization of the epithelium at 1000 µM. When the epithelium was pretreated for three minutes with the sodium channel blocker amiloride, the methacholine (1000µM)-induced JG increased to 0.67±0.09 µl/min/cm2 and the hyperpolarization increased to 2.2±0.5 mV over the amiloride-pretreated level. When pretreated for three minutes with the chloride channel blocker diphenylamine-2-carboxylic acid (DPC), the methacholine (1000µM)-induced JG was inhibited to 0.20±0.06 µl/min/cm2 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.




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