Cellular mechanism underlying oxytocin-stimulated Cl^- secretion in rat cauda epididymal epithelium.

The neurohypophyseal hormone oxytocin (OT) plays critical roles in lactation and parturition, while its function in male reproduction system is largely unknown. This study aims to investigate the effect of OT on regulating transepithelial ion transport in rat cauda epididymal epithelium. With the use of RT-PCR, Western blot, and immunohistochemical analysis, we found that OT receptor (OTR) was expressed and localized at the basal membrane of rat cauda epididymal epithelium. The short-circuit current (I_sc) measurement showed that basolateral application of OT to the primary cultured rat cauda epididymal epithelial cells elicited an increase in I_sc, which was abrogated by pretreating the epithelial cells with CFTR_inh-172, a blocker of cystic fibrosis transmembrane conductance regulator (CFTR). Pretreatment with the prostaglandin H synthase inhibitors indomethacin and piroxicam, or the nonselective antagonists of prostaglandin E2 (PGE₂) receptor EP2 or EP4, AH-6809, and AH-23848, significantly attenuated OT-stimulated I_sc response. Furthermore, the generation of PGE₂ was measured using enzyme-linked immunosorbent assay, demonstrating that OT induced a substantial increase in PGE₂ release from primary cultured rat cauda epididymal epithelial cells. In conclusion, activation of OTR by OT triggered PGE₂ release, resulting in CFTR-dependent Cl^- secretion through paracrine/autocrine pathways in rat cauda epididymal epithelium.

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