Cellular mechanisms of adrenaline-stimulated anion secretion by the mouse endometrial epithelium

The uterine fluid composition is largely determined by the absorptive and secretory activities of the endometrial epithelium. The present study explored the cellular mechanisms involved in adrenaline-stimulated anion secretion across the cultured mouse endometrial epithelium using the short-circuit current (ISC) technique in conjunction with transporter inhibitors and channel blockers. Cultured endometrial epithelial monolayers responded to basolateral application of adrenaline with an increase in ISC, which was attributable to both Cl- and HCO3- secretion. When extracellular Cl- or HCO3- was removed, the adrenaline-induced response, as measured by the total charge transfer per unit area, was reduced to 53% and 46%, respectively. When both Cl- and HCO3- were absent from the bathing solutions, the adrenaline-induced response was reduced to only 2% of the response when both ions were present, indicating substantial contribution of Cl- and HCO3- secretion to the adrenaline-stimulated response. Cellular mechanisms, e.g., transporters and ion channels, involved in Cl- or HCO3- secretion were investigated separately. Cl- secretion was found to depend on the activities of basolaterally located Na+-K+-ATPase, Na+-K+-2Cl- cotransporter, and K+ channels, while evidence suggested that HCO3- secretion depends substantially on basolaterally situated Na+-HCO3- cotransporter and Na+-H+ exchanger. Similar to what was seen for Cl- exit, a large portion of HCO3- appeared to exit apically through anion channels. The results indicate that the uterine fluid composition in the mouse may be regulated by adrenaline through stimulation of both Cl- and HCO3- secretion and may be fine-tuned through an elaborate operation of different cellular mechanisms.