Regulation of chloride secretion across porcine endometrial epithelial cells by prostaglandin E2

The endometrial epithelium consists of a surface epithelium which faces the uterine lumen and a glandular epithelium which invaginates into the endometrial stroma (Davis & Blair, 1993). The endometrium is responsible for the transfer of nutrients, fluid and electrolytes between the circulatory system and the uterine lumen. The transport-related activity of the surface and glandular epithelium provides an optimal intrauterine environment for implantation and embryo development. Previous studies of uterine fluid ionic composition from pigs, humans and rats have revealed that the K+ concentration is 4- to 5-fold higher than that in plasma, and the Na+ concentration is significantly lower than its concentration in plasma (Clemetson, Kim, Mallikarjuneswara & Wilds, 1972; Iritani, Sato & Nishikawa, 1974; Casslen & Nilsson, 1984). Regulation of Na+ and K+ concentrations within uterine and oviduct fluids appears to be important for reproductive events including sperm capacitation, acrosomal reaction, sperm-egg fusion and implantation of the developing embryo (Clemetson et al. 1972; Boldt, Casas, Whaley, Creazzo & Lewis, 1991; Fraser, 1992, 1995). Other important functions of endometrial epithelial cells include regulation of luminal pH and uterine fluid volume. Active secretion of Cl− and HCO3− ions has been shown to establish a driving force for fluid secretion and to regulate luminal fluid pH in the intestine (Wenzl, Sjaastad, Weintraud & Machen, 1989; MacLeod, Redican, Lembessis, Hamilton & Field, 1996) and airways (Smith & Welsh, 1992). In rabbit, fluid secretion into the oviduct lumen is driven by active secretion of Cl− across the oviduct epithelium (Leese, 1988). Previous studies using primary cultures of human endometrial epithelial cells grown on permeable supports demonstrated that amiloride-sensitive Na+ absorption was accompanied by K+ secretion across the cell monolayers (Matthews, Thomas, Redfern & Hirst, 1993). Other studies with primary cultures of rodent endometrial epithelial cells grown on permeable supports showed that the short circuit current was stimulated by forskolin, an activator of adenylyl cyclase (Rochwerger, Dho, Parker, Foskett & Buchwald, 1994; Leung, Wong, Gabriel, Yankaskas & Boucher, 1995). In cultured mouse endometrial cells, adrenergic agonists were shown to produce an increase in Isc that was consistent with anion secretion. This response was mediated by β-adrenergic receptors and was blocked by apical addition of either glibenclamide or diphenylamine 2,2′-dicarboxylic acid (DPC) (Chan, Fong, Chung & Wong, 1997). These experiments indicate that endometrial epithelial cells in culture are capable of both Na+ absorption and anion secretion. Prostaglandins are produced by epithelial and stromal endometrial cells in human and other species (Alecozay, Harper, Scheken & Hanahan, 1991; Zhang, Paria & Davis, 1991; Chen, Yang, Hilsenrath, Le & Harper, 1995). They act in both an endocrine and paracrine manner to increase uterine blood flow, vascular permeability and to regulate menstruation and implantation (Ford, Reynolds & Magness, 1982; Keys, King & Kennedy, 1986; Chaudhuri, 1991; Yee & Kennedy, 1993). Prostaglandins, specifically PGE2, have been shown to regulate electrolyte transport function in rabbit cortical collecting duct (Sakairi & Jacobson, 1995), prairie dog gallbladder (Saunders-Kirkwood, Cates & Roslyn, 1993) and porcine distal colon epithelium (Traynor, Brown & O'Grady, 1993). However, little is known about the transport-related actions of prostaglandins on endometrial epithelial cells. Recent studies with porcine surface endometrium using amphotericin B-permeabilized tissues showed that PGF2α increased Na+ absorption by activation of K+ channels in the basolateral membrane (Vetter & O'Grady, 1996). The aim of this study was to characterize the transport properties of porcine glandular epithelial cells and to investigate the effect of PGE2 on regulation of anion transport.