Tetrodotoxin does not block the epithelium-dependent release of prostaglandin E2 induced by electrical field stimulation in isolated ferret trachea.
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.
Ullman
A
A
Department of Clinical Pharmacology, Gothenburg University, Sweden.
Ciabattoni
G
G
Svedmyr
N
N
Skoogh
B E
BE
Löfdahl
C G
CG
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
D013779:Tetrodotoxin; D015121:6-Ketoprostaglandin F1 alpha; D001285:Atropine; D015232:Dinoprostone