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

• Published in: American Journal of Physiology: Cell Physiology 2020-10, Vol.319 (4), p.C630-C640
• Main Authors: Gao, Dong-Dong, Wang, Long-Long, Xu, Jia-Wen, Qiu, Zhuo-Er, Zhu, Yun-Xin, Zhang, Yi-Lin, Zhou, Wen-Liang
• Format: Article
• Language: English
• Subjects: Animals; Antagonists; Autocrine Communication - drug effects; Autocrine signalling; Biphenyl Compounds - pharmacology; Cell activation; Conductance; Cyclooxygenase Inhibitors - pharmacology; Cystic fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Dinoprostone - genetics; Enzyme-linked immunosorbent assay; Epididymis - drug effects; Epididymis - metabolism; Epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelium; Female; Gene Expression Regulation - drug effects; Indomethacin; Lactation; Lactation - genetics; Male; Oxytocin; Oxytocin - genetics; Paracrine Communication - drug effects; Paracrine signalling; Parturition; Piroxicam; Pituitary (posterior); Polymerase chain reaction; Primary Cell Culture; Prostaglandin E2; Prostaglandin H synthase; Rats; Receptors, Oxytocin - genetics; Short-circuit current
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00397.2019

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 ( ) measurement showed that basolateral application of OT to the primary cultured rat cauda epididymal epithelial cells elicited an increase in , which was abrogated by pretreating the epithelial cells with CFTR -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 (PGE ) receptor EP2 or EP4, AH-6809, and AH-23848, significantly attenuated OT-stimulated response. Furthermore, the generation of PGE was measured using enzyme-linked immunosorbent assay, demonstrating that OT induced a substantial increase in PGE release from primary cultured rat cauda epididymal epithelial cells. In conclusion, activation of OTR by OT triggered PGE release, resulting in CFTR-dependent Cl secretion through paracrine/autocrine pathways in rat cauda epididymal epithelium.