Cellular Mechanism Underlying Oxytocin-Stimulated Cl - Secretion in Rat Cauda Epididymal Epithelium.

The neurohypophyseal hormone oxytocin (OT) plays critical roles in lactation and parturition, whilst 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. Using 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 (ISC ) measurement showed that basolateral application of OT to the primary cultured rat cauda epididymal epithelial cells elicited an increase in ISC , which was abrogated by pretreating the epithelial cells with CFTRinh -172, a blocker of cystic fibrosis transmembrane conductance regulator (CFTR). Pretreatment with the prostaglandin H synthase (PGHS) inhibitors indomethacin and piroxicam, or the non-selective antagonists of PGE2 receptor EP2 or EP4, AH-6809 and AH-23848, significantly attenuated OT-stimulated ISC response. Furthermore, the generation of prostaglandin E2 (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.