This Article Full Text Full Text (PDF) All Versions of this Article: 2007-0117OCv1 38/1/88    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Seto, V. Articles by Janssen, L. J. Search for Related Content PubMed PubMed Citation Articles by Seto, V. Articles by Janssen, L. J.

E-Ring Isoprostanes Stimulate a Cl^– Conductance in Airway Epithelium via Prostaglandin E₂-Selective Prostanoid Receptors

¹ Firestone Institute for Respiratory Health, St. Joseph's Healthcare, and Department of Medicine, McMaster University, Hamilton, Ontario, Canada

Correspondence and requests for reprints should be addressed to Dr. L. J. Janssen, L-314, St. Joseph's Hospital, 50 Charlton Ave. East, Hamilton, ON, L8N 4A6 Canada. E-mail: janssenl{at}mcmaster.ca

Isoprostanes comprise a class of membrane lipid metabolites produced during oxidative stress, including asthma, chronic obstructive pulmonary disease, and cystic fibrosis. They are widely recognized to evoke a variety of biological responses in airway and pulmonary vascular smooth muscle, lymphatics, and innervation. However, their effects on airway epithelium are largely unstudied. We examined the electrophysiological responses evoked by several different isoprostane species in bovine airway epithelium using the Ussing chamber technique. The E-ring isoprostanes 15-E_1t-IsoP and 15-E_2t-IsoP evoked a substantial increase in short-circuit current (I_SC), whereas four different F-ring isomers were ineffective. 15-E_2t-IsoP–evoked I_SC was mimicked by the prostaglandin E₂-selective prostanoid receptor (EP)-agonist prostaglandin E₂ but not by agonists of EP₁/EP₃-, FP-, or TP receptors (sulprostone, fluprostenol, and U46619, respectively). This response was significantly reduced by the EP₄-receptor blocker GW627386 but not by blockers of other prostanoid receptors (ICI 192,605 [TP-selective], SC19220 [EP₁-selective], AH6809 [DP/EP₁/EP₂-selective], and AL8810 [FP-selective]). 15-E_2t-IsoP–evoked I_SC was reduced by blockers of Cl^– channels (niflumic acid and 5-nitro-2-(3-phenylpropylamino)-benzoic acid), of Na⁺/K⁺/2Cl^– co-transport (furosemide and bumetanide), of adenylate cyclase (MDL 12,330A), or of guanylate cyclase (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) but not by blockers of Na⁺ conductances (amiloride). We conclude that 15-E_2t-IsoP activates a transepithelial Cl^– conductance in bovine airway epithelium through an EP₄ receptor coupled to adenylate cyclase and soluble guanylate cyclase.

Key Words: chloride conductance • isoprostane • oxidative stress • prostanoid receptor • secretion

CLINICAL RELEVANCE This article provides the first description of the physiological response of native airway epithelium to isoprostanes, a novel class of inflammatory mediators. There is only one other such report in which cultured epithelial cells were used.

 

This article has been cited by other articles:

				C. Paredes, T. Tazzeo, and L. J. Janssen E-Ring Isoprostane Augments Cholinergic Neurotransmission in Bovine Trachealis via FP Prostanoid Receptors Am. J. Respir. Cell Mol. Biol., December 1, 2007; 37(6): 739 - 747. [Abstract] [Full Text] [PDF]