MEDICAL HYPOTHESES AND RESEARCH
VOL. 2, No. 4, October 2005
E. Peddle and L. J. Janssen  Med Hypotheses Res 2: 573-579.
E-Ring Isoprostanes Evoke Chloride Current in Bovine
Emily Peddle and Luke J. Janssen*
Abstract. Isoprostanes are produced from membrane lipids by free radicals, and
accumulate to substantial degrees in many diseases including asthma, chronic obstructive
pulmonary disorder and cystic fibrosis. They are now recognized to evoke a variety of
biological responses from airway and pulmonary vascular smooth muscle, lymphatics and
innervation. However, their effects on airway epithelium are largely unstudied. Isoprostane-
mediated electrophysiological responses were monitored in bovine bronchial epithelium
using the Ussing chamber technique. E-ring isoprostanes (8-iso-PGE1 and 8-iso-PGE2)
evoked a large increase in short-circuit current (ISC) which was sensitive to chloride channel
blockers; the F-ring isoprostane (8-iso-PGF2α) had no effect. The response to 8-iso-PGE2
was insensitive to the TP-receptor blocker ICI 192605 and not mimicked by the TP-receptor
agonist U46619; it also was insensitive to the EP1-receptor blocker AH 6809, even though
prostaglandin E2 evoked a similar response as 8-iso-PGE2. We conclude that E-ring
isoprostanes activate a transepithelial chloride conductance in bovine bronchial epithelium
through a non-TP receptor which may be of the EP subtype.
*Address all correspondence to: Dr. L. J. Janssen, L-314, St. Joseph’s Hospital,
50 Charlton Ave. East, Hamilton, Ontario, Canada L8N 4A6.
Phone: 905-522-1155 (ext. 5912). FAX: 905-540-6510.
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