Regulation of anion secretion by prostaglandin E2 in the mouse endometrial epithelium

The present study was an investigation of the regulation of anion secretion across cultured mouse endometrial epithelium by prostaglandin E-2 (PGE(2)) using the short-circuit current (I-sc) technique. The cultured endometrial monolayers responded to both apical and basolateral application of PGE(2) with a sustained rise in I-sc in a concentration-dependent manner. However, the potencies of apical and basolateral addition of PGE(2) were different, with apparent EC50 of 200 and 4 nM, respectively. Replacement of Cl- or HCO3- in the bathing solution significantly reduced the I-sc responses to both apical and basolateral addition of PGE(2); however, the apical response exhibited greater dependence on HCO3-. Pretreatment with diphenylamine 2,2'-dicarboxylic acid, a Cl- channel blocker, significantly reduced both PGE(2)-induced I-sc responses, while pretreatment with amiloride, a Na+ channel blocker, did not exert any effect. Forskolin, an adenylate cyclase activator, and 3-isobutyl-dihydro-testosterone-1-methyl-xanthine, a cAMP phosphodiesterase inhibitor, mimicked the I-sc response to PGE(2) while MDL12330A, an adenylate cyclase inhibitor, completely abolished the PGE(2)-induced I-sc. The results of the present study indicate that the anion secretion across the mouse endometrial epithelium may be regulated by PGE(2) involving a cAMP-dependent mechanism predominantly. The differential responses to apical and basolateral challenge with PGE(2) also suggest that PGE(2) of different origins may play different roles in uterine function.