Characterization of prostanoid receptors mediating contraction of the gastric fundus and ileum: studies using mice deficient in prostanoid receptors

Authors


Department of Pharmacology, Asahikawa Medical College, Midorigaoka-Higashi 2-1-1-1, Asahikawa 078-8510, Japan. E-mail: ushikubi@asahikawa.med.ac.jp

Abstract

  • Receptors mediating prostanoid-induced contractions of longitudinal sections of gastric fundus and ileum were characterized by using tissues obtained from mice deficient in each type and subtype of prostanoid receptors.

  • The fundus and ileum from mice deficient in either EP3 (EP3−/− mice), EP1 (EP1−/− mice) and FP (FP−/− mice) all showed decreased contraction to PGE2 compared to the tissues from wild-type mice, whereas contraction of the fundus slightly increased in EP4−/− mice.

  • 17-phenyl-PGE2 also showed decreased contraction of the fundus from EP3−/−, EP1−/− and FP−/− mice. Sulprostone showed decreased contraction of the fundus from EP3−/− and FP−/− mice, and decreased contraction of the ileum to this compound was seen in tissues from EP3−/−, EP1−/− and FP−/− mice. In DP−/− mice, sulprostone showed increased contraction.

  • DI-004 and AE-248 caused the small but concentration-dependent contraction of both tissues, and these contractions were abolished in tissues obtained from EP1−/− and EP3−/− mice, respectively, but not affected in other mice.

  • Contractions of both fundus and ileum to PGF2α was absent at lower concentrations (10−9 to 10−7 M), and suppressed at higher concentrations (10−6 to 10−5 M) of the agonist in the FP−/− mice. Suppression of the contractions at the higher PGF2α concentrations was also seen in the fundus from EP3−/−, EP1−/− and TP−/− mice and in the ileum from EP3−/− and TP−/− mice.

  • Contraction of the fundus to PGD2 was significantly enhanced in DP−/− mice, and contractions of the fundus and ileum to this PG decreased in FP−/− and EP3−/− mice.

  • Contractions of both tissues to I-BOP was absent at 10−9 to 10−7 M and much suppressed at higher concentrations in TP−/− mice. Slight suppression to this agonist was also observed in the tissues from EP3−/− mice.

  • PGI2 induced small relaxation of both tissues from wild-type mice. These relaxation reactions were much potentiated in EP3−/− mice. On the other hand, significant contraction to PGI2 was observed in both tissues obtained from IP−/− mice.

  • These results show that contractions of the fundus and ileum induced by each prostanoid agonist are mediated by actions of this agonist on multiple types of prostanoid receptors and in some cases modified by its action on relaxant receptors.

British Journal of Pharmacology (2000) 131, 745–755; doi:10.1038/sj.bjp.0703627

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