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 Ca¹⁺ 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.