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

Abstract

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 (J(G)) 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 microA/cm(2), as measured by the Ussing technique. The secretagogue methacholine induced concentration-dependent increases in J(G) after 3 min from 0.003 microl. min(-1). cm(-2) at 0.1 microM to 0.41 +/- 0.04 microl. min(-1). cm(-2) at 1,000 microM, with a 0.9 +/- 0.1 mV hyperpolarization of the epithelium at 1,000 microM. When the epithelium was pretreated for 3 min with the sodium channel blocker amiloride, the methacholine (1,000 microM)-induced J(G) increased to 0.67 +/- 0.09 microl. 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 microM)-induced J(G) was inhibited to 0.20 +/- 0.06 microl. min(-1). cm(-2), and the methacholine-induced hyperpolarization was abolished. These data indicate that, in porcine airways, methacholine-induced J(G) may be increased by inhibition of sodium absorption and decreased by inhibition of chloride secretion.

Bioelectric Properties of Chloride Channels in Human, Pig, Ferret, and Mouse Airway Epithelia

“…However, the kinetics of NPPB inhibition in the pig was notably slower than in all other species. These findings support previous studies on submucosal gland secretion in the pig trachea, in which NPPB inhibited methacholineand acetylcholine-induced glandular secretions more effectively than glibenclamide (25,44).…”

Mechanisms of anion secretion in Calu‐3 human airway epithelial cells by 7,8‐benzoquinoline

“…However, when potassium channel activation increases anion secretion, hyperpolarisation also promotes electrogenic sodium absorption ( Gao et al , 2001 ) and hence is profluid absorption. While this is so for the surface airway epithelium, it cannot apply to the Calu‐3 monolayers since no pathway for electrogenic sodium absorption exists, although the evidence for submucous glands themselves remains open ( Phillips et al , 2002 ).…”

Liquid secretion properties of airway submucosal glands

“…mRNA for both α and β subunits of epithelial Na + channels (ENaC) are expressed in human gland ducts, and it has been suggested that these channels might be involved in the absorption of salt and water (Burch et al 1995). This notion is supported by observations that amiloride, an ENaC inhibitor, increases the rate of ACh-induced fluid secretion in porcine tracheal glands by 60% (Phillips et al 2002b).…”