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First published on July 29, 2005; DOI: 10.1124/jpet.105.088542

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Received for publication May 13, 2005.
Revised July 20, 2005.
Accepted for publication July 26, 2005.

Prostanoids secreted by alveolar macrophages enhance ionic currents in swine tracheal submucosal gland cells

Huilling Liu 1, Abulkhair Mamoon 1, Jerry M. Farley 1*

1 University of Mississippi Medical Center

* Address correspondence to: E-mail: jfarley{at}pharmacology.umsmed.edu

Abstract

We examined the effect of substances released by swine alveolar macrophages (AM) on ionic currents in airway submucosal gland cells (SGC). AM obtained by lavage were activated by 24-hour zymosan exposure (0.1 mg/ml). Supernatant was collected and used to stimulate short circuit current changes ({Delta}ISC) in SGC monolayers in Ussing chambers. Dexamethasone (1 µM) or indomethacin (5 µM) during zymosan exposure of AM reduced or abolished the supernatant-induced {Delta}ISC. Zymosan exposure induced a 5-fold increase in cyclooxygenase (COX)-2 but not COX-1 protein levels in AM. PGE2 concentration in the supernatant from zymosan-activated AM was 550 ± 10 nM (n=3) compared with 28 ± 3 nM for unstimulated AM (n=3). PGE2, applied serosally, induced {Delta}ISC with an EC50 of 15.5 ± 1.3 nM (n=4), and 3.6 ± 1.8 µM (n=3) when applied apically. Four types of endoprostanoid receptors (EP1~4) were detected in SGC using Western blot. PGE2-induced {Delta}ISC were inhibited by 6-isopropoxy-9-oxoxanthene-2-carboxylic acid (AH6809), but not by 8-chloro-dibenzo[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-acetylhydrazide (SC19220), suggesting that EP2 but not EP1 receptors were activated by PGE2. Pretreatment of SGC with supernatant from zymosan-activated AM, PGE2, or forskolin enhanced the sensitivity to acetylcholine (ACh)-induced {Delta}ISC. PGE2-induced {Delta}ISC were blocked by charybdotoxin (ChTX), chromanol 293B or glibenclamide, ACh-induced {Delta}ISC were only blocked by ChTX or glibenclamide. None of these blockers altered PGE2 pretreatment-induced sensitization of ACh-induced {Delta}ISC. These results demonstrate that prostanoids released from activated-AM directly increase CFTR and K+ channel activity. ACh-induced {Delta}ISC are also enhanced due to enhanced activation of Ca2+-activated K+ channels (KCa).


Key words: airway, current, macrophage, prostaglandin, sensitization, submucousal


This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
H. Liu and J. M. Farley Sr.
Prostaglandin E2 Enhances Acetylcholine-Induced, Ca2+-Dependent Ionic Currents in Swine Tracheal Mucous Gland Cells
J. Pharmacol. Exp. Ther., August 1, 2007; 322(2): 501 - 513.
[Abstract] [Full Text] [PDF]


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