title: Tetrodotoxin does not block the epithelium-dependent release of prostaglandin E2 induced by electrical field stimulation in isolated ferret trachea.
abstract: Electrical field stimulation (EFS) has previously been shown to induce the release of prostaglandin (PG) E2 from ferret tracheal epithelium. We have now conducted a study to see whether this effect of EFS is due to the activation of nerves or whether it is a non-neural effect. The release of PGE2 and 6-keto-PGF1 alpha into the bath fluid was assayed in isolated ferret tracheas with (E+) or without (E-) epithelium, stimulated by either EFS or direct vagal nerve stimulation (DNS) repeatedly for 120 min. EFS-stimulated E+ preparations showed a gradual decline in the contractile responses (30 +/- 1% of baseline) and an increase in PGE2 to 296 +/- 38 pg/ml. In EFS-stimulated, epithelium-denuded (E-) preparations, the decline was significantly lower (11 +/- 5%), as well as the final concentration of PGE2 (107 +/- 21 pg/ml). In DNS-stimulated E+ preparations, the contraction decline was 8 +/- 1% and the final concentration of PGE2 was less than 6 pg/ml. Although tetrodotoxin (TTX) abolished the contractile response in EFS-stimulated E+ preparations, it did not significantly reduce the release of PGE2 (260 +/- 6 pg/ml), whereas atropine partly counteracted the release. The bath concentration of 6-keto-PGF1 alpha increased, independently of the electrical stimulation, contractile response, or presence of the epithelium. We conclude that EFS activates the epithelium-dependent release of PGE2 by a TTX-resistant mechanism. This may be due to an activation of TTX-resistant nerves, or possibly to a non-neural effect, such as a direct effect on the epithelial cells. The results indicate that the airway epithelium has the ability to respond to certain stimuli with a pronounced release of PGE2, thereby counteracting bronchoconstriction.
authors.affiliation: Department of Clinical Pharmacology, Gothenburg University, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Ullman
authors.forename: G
authors.initials: G
authors.lastname: Ciabattoni
authors.forename: N
authors.initials: N
authors.lastname: Svedmyr
authors.forename: B E
authors.initials: BE
authors.lastname: Skoogh
authors.forename: C G
authors.initials: CG
authors.lastname: Löfdahl
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004558:Electric Stimulation; D004848:Epithelium / Q000378:metabolism; D005289:Ferrets; D066298:In Vitro Techniques; D013779:Tetrodotoxin / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
chemical_list: D013779:Tetrodotoxin; D015121:6-Ketoprostaglandin F1 alpha; D001285:Atropine; D015232:Dinoprostone