Prostaglandin D2 increases Cl secretion across canine tracheal epithelium through cyclo-oxygenase stimulation and cAMP production.
Prostaglandin (PG) D2 is one cyclo-oxygenase product of arachidonic acid metabolites that may play a role in the pathogenesis of asthma. To determine the effect of PGD2 on ion transport by airway epithelium and its mechanism of action, we measured bioelectric properties of canine cultured tracheal epithelium under short-circuit conditions in vitro. PGD2 (10(-7) M) increased short-circuit current (Isc) from 5.5 +/- 1.2 to 14.1 +/- 2.9 microA cm-2 (means +/- SE, P less than 0.01) when added to the mucosal solution, and to 22.2 +/- 3.8 microA cm-2 (P less than 0.001) when added to the submucosal solution, an effect that was accompanied by the corresponding increases in transepithelial potential difference and conductance. These effects were dose-dependent. The PGD2-induced increase in Isc was not altered by preincubation of cells with autonomic antagonists (phentolamine, propranolol, atropine), the lipoxygenase inhibitor AA-861, the protein kinase C inhibitor H-7, or the Na channel blocker amiloride, but it was inhibited by each of indomethacin, piroxicam, the Cl channel blocker diphenylamine-2-carboxylate, the Cl transport inhibitor furosemide, and Cl-free medium. Intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels were dose-dependently increased by PGD2. These results suggest that PGD2 may selectively stimulate airway epithelial Cl secretion via cyclo-oxygenase- and cAMP-dependent pathway.
Tamaoki
J
J
First Department of Medicine, Tokyo Women's Medical College, Japan.
Kanemura
T
T
Sakai
N
N
Isono
K
K
Chiyotani
A
A
Yamauchi
F
F
Takizawa
T
T
Konno
K
K
D000818:Animals; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis; D004285:Dogs; D004563:Electrochemistry; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D015230:Prostaglandin D2 / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism
D018118:Chloride Channels; D002712:Chlorides; D008565:Membrane Proteins; D000242:Cyclic AMP; D011451:Prostaglandin-Endoperoxide Synthases; D015230:Prostaglandin D2