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http://purl.uniprot.org/citations/10535876http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10535876http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10535876http://www.w3.org/2000/01/rdf-schema#comment"

Background & aims

To examine the involvement of EP(3) receptors in physiological regulation of duodenal HCO(3)(-) secretion, we disrupted the gene encoding EP receptors in mice by homologous recombination and evaluated acid-induced HCO(3)(-) secretion, which is physiologically important in the mucosal defense against acid injury, using EP(1)- and EP(3)-receptor knockout mice.

Methods

The experiments were performed in the following 3 groups of mice after 18 hours of fasting: wild-type [WT (+/+)] mice, EP(1)-receptor knockout [EP(1) (-/-)] mice, and EP(3)-receptor knockout [EP(3) (-/-)] mice. Under urethane anesthesia, the proximal duodenal loop was perfused with saline that was gassed with 100% O(2), heated at 37 degrees C, and kept in a reservoir, and HCO(3)(-) secretion was measured at pH 7.0 using a pH-stat method and by adding 5 mmol/L HCl.

Results

The duodenum of WT (+/+) mice increased HCO(3)(-) secretion in response to luminal perfusion of prostaglandin E(2) and forskolin as well as mucosal acidification. The latter effect was significantly inhibited by prior administration of indomethacin. HCO(3)(-) response to acid was observed in EP(1) (-/-) mice but disappeared totally in EP(3) (-/-) animals, although the acidification increased mucosal PGE(2) generation by similar degrees in all groups. The HCO(3)(-) stimulatory action of PGE(2) was also absent in EP(3) (-/-) but not EP(1) (-/-) mice, but forskolin effect was observed in both groups of animals, similar to WT (+/+) mice. Perfusion of the duodenum with 20 mmol/L HCl for 4 hours caused severe damage in EP(3) (-/-) mice and WT (+/+) animals pretreated with indomethacin, but not in EP(1) (-/-) mice.

Conclusions

The presence of EP(3)-receptors is essential for maintaining duodenal HCO(3)(-) secretion and mucosal integrity against luminal acid."xsd:string
http://purl.uniprot.org/citations/10535876http://purl.org/dc/terms/identifier"doi:10.1016/s0016-5085(99)70398-7"xsd:string
http://purl.uniprot.org/citations/10535876http://purl.org/dc/terms/identifier"doi:10.1016/s0016-5085(99)70398-7"xsd:string
http://purl.uniprot.org/citations/10535876http://purl.uniprot.org/core/author"Kato S."xsd:string
http://purl.uniprot.org/citations/10535876http://purl.uniprot.org/core/author"Kato S."xsd:string
http://purl.uniprot.org/citations/10535876http://purl.uniprot.org/core/author"Narumiya S."xsd:string
http://purl.uniprot.org/citations/10535876http://purl.uniprot.org/core/author"Narumiya S."xsd:string
http://purl.uniprot.org/citations/10535876http://purl.uniprot.org/core/author"Takeuchi K."xsd:string
http://purl.uniprot.org/citations/10535876http://purl.uniprot.org/core/author"Takeuchi K."xsd:string
http://purl.uniprot.org/citations/10535876http://purl.uniprot.org/core/author"Sugimoto Y."xsd:string
http://purl.uniprot.org/citations/10535876http://purl.uniprot.org/core/author"Sugimoto Y."xsd:string
http://purl.uniprot.org/citations/10535876http://purl.uniprot.org/core/author"Araki H."xsd:string
http://purl.uniprot.org/citations/10535876http://purl.uniprot.org/core/author"Araki H."xsd:string
http://purl.uniprot.org/citations/10535876http://purl.uniprot.org/core/author"Ichikawa A."xsd:string
http://purl.uniprot.org/citations/10535876http://purl.uniprot.org/core/author"Ichikawa A."xsd:string
http://purl.uniprot.org/citations/10535876http://purl.uniprot.org/core/author"Ushikubi F."xsd:string
http://purl.uniprot.org/citations/10535876http://purl.uniprot.org/core/author"Ushikubi F."xsd:string
http://purl.uniprot.org/citations/10535876http://purl.uniprot.org/core/author"Furukawa O."xsd:string
http://purl.uniprot.org/citations/10535876http://purl.uniprot.org/core/author"Furukawa O."xsd:string
http://purl.uniprot.org/citations/10535876http://purl.uniprot.org/core/author"Ukawa H."xsd:string
http://purl.uniprot.org/citations/10535876http://purl.uniprot.org/core/author"Ukawa H."xsd:string
http://purl.uniprot.org/citations/10535876http://purl.uniprot.org/core/date"1999"xsd:gYear
http://purl.uniprot.org/citations/10535876http://purl.uniprot.org/core/date"1999"xsd:gYear
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