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• W2094402172 startingPage "1352" @default.
• W2094402172 abstract "Background & Aims: Mucins form an integral part of innate host defenses against intestinal pathogens and irritants. However, the mechanisms whereby mucin secretion is regulated during inflammation are poorly understood. Because prostaglandin E2 (PGE2) is prominent during intestinal inflammation, we investigated its receptor-signaling pathway coupled to mucin exocytosis in the colonic epithelial cell line LS174T and rat colon. Methods: Reverse-transcription polymerase chain reaction (RT-PCR) and [3H]PGE2 binding assays were used to identify the PGE2 receptors (EP). Intracellular cyclic adenosine monophosphate ([cAMP]i) was quantified by enzyme immunoassay. Mucins were metabolically labeled with [3H]glucosamine, and mucin secretion was quantified by Sepharose 4B column chromatography, immunoblot analysis, and cesium chloride density gradient centrifugation. Results: RT-PCR and DNA sequence analysis identified EP2, EP3, and EP4 receptors. Mucin secretion and [cAMP]i production by LS174T cells were stimulated dose-dependently by PGE2, the EP4-receptor agonist 1-OH-PGE1, and the EP3/EP4 agonist M&B28767 and were inhibited with the adenylate cyclase inhibitor SQ22536. The EP1, EP2, and EP3/EP1-receptor agonists iloprost, butaprost, and sulprostone, respectively, had no effect. Similar results were obtained in rat colonic loop studies confirming that the EP4 receptor is linked to mucin exocytosis in vivo. [3H]PGE2 binding to cell membranes identified a high-affinity binding site that was competitively inhibited by M&B28767 (EP3/EP4) > 1-OH-PGE1 (EP4) > sulprostone (EP3/EP1) > butaprost (EP2). Conclusions: PGE2 coupling to the EP4 receptor stimulates [cAMP]i-dependent mucin exocytosis.GASTROENTEROLOGY 1999;117:1352-1362" @default.
• W2094402172 created "2016-06-24" @default.
• W2094402172 creator A5046370435 @default.
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• W2094402172 date "1999-12-01" @default.
• W2094402172 modified "2023-10-16" @default.
• W2094402172 title "Prostaglandin E2 stimulates rat and human colonic mucin exocytosis via the EP4 receptor" @default.
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• W2094402172 doi "https://doi.org/10.1016/s0016-5085(99)70285-4" @default.
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