[Effect of histamine on electrical properties of airway epithelium and its antagonism by azelastine].
To elucidate the mechanism of the action of histamine on bioelectric properties of the airway epithelium and the fact that the anti-allergic agent azelastine is possibly antagonistic to it, we studied canine cultured tracheal epithelium under short-circuit conditions in vitro. Addition of histamine to the submucosal but not mucosal bath of Ussing chamber increased short-circuit current (Isc) in a dose-dependent fashion, the maximal increase and the EC50 value being 5.7 +/- 0.9 microA/cm2 (mean +/- SE, p less than 0.001) and 3 x 10(-6) M, respectively. Pretreatment of tissues with pyrilamine abolished the histamine-induced increase in Isc (p less than 0.001), whereas cimetidine had no effect. In addition, the histamine action on Isc was effectively depressed by the Cl channel blocker diphenylamine-2-carboxylate, Cl-free medium, and indomethacin. The release of PGE2 and PGF2 alpha was significantly enhanced by the submucosal application of histamine. Pretreatment of tissues with azelastine dose-dependently attenuated the increase in Isc induced by 10(-4) M histamine. These results indicate that histamine increases the airway epithelial Isc via stimulation of prostaglandin synthesis and subsequent movement of Cl toward the lumen, and that azelastine may be useful in preventing histamine-induced water secretion in the airway.
Tamaoki
J
J
First Department of Medicine, Tokyo Women's Medical College.
Sakai
N
N
Isono
K
K
Kanemura
T
T
Takeyama
K
K
Takeuchi
S
S
Chiyotani
A
A
Takizawa
T
T
D000818:Animals; D002478:Cells, Cultured; D002713:Chlorine / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells; D006632:Histamine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists; D008564:Membrane Potentials / Q000187:drug effects; D010793:Phthalazines / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis; D014132:Trachea / Q000378:metabolism*
D006634:Histamine H1 Antagonists; D010793:Phthalazines; D011453:Prostaglandins; D002713:Chlorine; D006632:Histamine; C020976:azelastine