Effect of inflammatory mediators on the electrophysiology of the human oviduct

The effects of histamine and other inflammatory mediators on the electrophy siology and intracellular free calcium ([Ca2+](i)) of human oviductal epith elial cells, grown as a polarized layer in primary culture, were studied. T ransepithelial potential difference (PD) and short-circuit current (I-scc) were recorded using a modified Ussing chamber. Resistance (R) was calculate d 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 histam ine effect was reduced by triprolidine (H-1 receptor antagonist) but was un affected by H-2 (ranitidine) or H-3 (thioperamide) receptor antagonists, Bl ockers of Na+, K+, or Na+/K+/2Cl(-) channels did not affect histamine actio n. Blockers of Cl-/HCO3- channels or Ca2+ channels reduced the histamine ef fect, 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 inhibi ted histamine-stimulated [Ca2+](i) increase. Cimetidine, (H-2 receptor anta gonist), ranitidine, or thioperamide reduced the histamine effect. Histamin e increased contractions of both circular and longitudinal smooth muscles i n oviduct segments, an effect that was antagonized by triprolidine or thiop eramide but not by ranitidine, Histamine's action on Ca2+ and Cl- movements may adversely affect oviductal fluid production and decrease fertility. PA F's effects on Cl- movements may be important for normal embryo transport.