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Effect of Inflammatory Mediators on the Electrophysiology of the Human Oviduct¹

^a Department of Biology, University of York, York YO21 5YW, United Kingdom ^b The Princess Royal Hospital, Hull HU8 9HE, United Kingdom

The effects of histamine and other inflammatory mediators on the electrophysiology and intracellular free calcium ([Ca²⁺]_i) of human oviductal epithelial cells, grown as a polarized layer in primary culture, were studied. Transepithelial potential difference (PD) and short-circuit current (I_scc) were recorded using a modified Ussing chamber. Resistance (R) was calculated from the measurements of PD and I_scc. Basally applied histamine produced transient increases in PD and I_scc with a small decrease in R. The histamine effect was reduced by triprolidine (H₁ receptor antagonist) but was unaffected by H₂ (ranitidine) or H₃ (thioperamide) receptor antagonists. Blockers of Na⁺, K⁺, or Na⁺/K⁺/2Cl^- channels did not affect histamine action. Blockers of Cl^-/HCO₃^- channels or Ca²⁺ channels reduced the histamine effect. Platelet activating factor (PAF), applied apically, increased PD and I_scc. Histamine produced a transient increase in fluorescence of Fura 2-AM dye, indicating an increase in [Ca²⁺]_i. Triprolidine pretreatment inhibited histamine-stimulated [Ca²⁺]_i increase. Cimetidine, (H₂ receptor antagonist), ranitidine, or thioperamide reduced the histamine effect. Histamine increased contractions of both circular and longitudinal smooth muscles in oviduct segments, an effect that was antagonized by triprolidine or thioperamide but not by ranitidine. Histamine's action on Ca²⁺ and Cl^- movements may adversely affect oviductal fluid production and decrease fertility. PAF's effects on Cl^- movements may be important for normal embryo transport.

¹ Supported by the Wellcome Trust, Grant No. 049008/Z/96/Z.

² Correspondence: S.J. Downing, Department of Biology, University of York, PO Box No. 373, York YO21 5YW, UK. FAX: 44 1904 432860; sjd13{at}york.ac.uk

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