Kinin and histamine stimulate Cl- secretion in gerbil middle ear epithelium: connection to otitis media.
The effects of bradykinin (BK) and histamine on transepithelial ion transport in primary cultures of gerbil middle ear epithelium were investigated. Lysyl-bradykinin (lys-BK) elicited a transient increase in short-circuit current (I(sc)) when added to apical or basolateral surfaces. Lys-BK had a larger effect than BK or des-arg9-BK on both epithelial surfaces. Histamine induced a transient increase in I(sc) only when added to the basolateral surface. Mepyramine, an H1 histamine antagonist, greatly reduced the histamine-induced I(sc). The H2 and H3 histamine antagonists were both ineffective for inhibiting the I(sc) responses to histamine. Diphenylamine-2-carboxylate or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, Cl- channel blockers, significantly blocked the I(sc) responses to lys-BK or histamine. The Ca2+-mobilizing action of lys-BK and histamine was also investigated in single middle ear epithelial cells. BK and histamine induced an increase in the intracellular Ca2+ concentration. 1,2-Bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester, a calcium chelator, greatly reduced the increase in the I(sc) responses to lys-BK or histamine. These data indicate that BK and histamine activate intracellular Ca2+-dependent mechanisms, leading to apical Cl- secretion in the cultured gerbil middle ear epithelium via B2 BK receptors and H1 histamine receptors.
Department of Otorhinolaryngology, Tohoku University School of Medicine, Sendai, Japan. furukawa@orl.med.tohoku.ac.jp
M
M
Furukawa
H
H
Suzuki
K
K
Ikeda
T
T
Oshima
M
M
Yamaya
H
H
Sasaki
T
T
Takasaka
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D004432:Ear, Middle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004553:Electric Conductivity; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006632:Histamine / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism; D007477:Ions; D007609:Kallidin / Q000494:pharmacology; D009994:Osmolar Concentration; D010033:Otitis Media / Q000209:etiology; D018002:Receptors, Bradykinin / Q000502:physiology; D011968:Receptors, Histamine / Q000502:physiology
D002614:Chelating Agents; D002712:Chlorides; D007477:Ions; D018002:Receptors, Bradykinin; D011968:Receptors, Histamine; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D007609:Kallidin; D004533:Egtazic Acid; D006632:Histamine; D001920:Bradykinin; D002118:Calcium