EP4 and EP2 receptor subtypes involved in colonic secretion in rat

The study was designed to determine the prostaglandin EP receptor subtypes functionally involved in electrogenic ion secretion in rat colon. With 30 rats, measurements of short circuit current (SCC) and slope conductance were obtained by Ussing chamber technique. Prostaglandin E2 (PGE(2)) and other EP receptor selective agonists were employed on stripped rat colon pre-treated with indomethacin and theophylline. Receptor-specific agonists were butaprost (EP2), sulprostone (EP1 and EP3) and PGE(1) alcohol (OH-PGE(1)) (EP4). GW627368X was used as a specific EP4 receptor antagonist. Forskolin-induced SCC was used as a control of tissue viability. The mean basal SCC was 24.5 +/- 0.9 mu A/cm(2) (range 9.8-45.1), and mean basal slope conductance was 23.7 +/- 6.1 mS/cm(2) (range 9.7-39.8). The basal SCC decreased after pre-treatment with indomethacin and increased after pre-treatment with theophylline. PGE(2), butaprost and OH-PGE(1) stimulated maximal increase in SCC (55.8 +/- 4.1, 43.9 +/- 3.8 and 93.9 +/- 2.7 mu A/cm(2), respectively), while sulprostone had no apparent effects. GW627368X eliminated OH-PGE(1)-induced SCC and partially PGE(2)-induced SCC, leaving butaprost-induced SCC almost unperturbed. Bumetanide, 20 mu M, inhibited between 40% and 80% of the agonist-induced changes in SCC. In conclusion, compilation of the results on induced SCC by subtype specific receptor agonists for EP receptors and the pattern of induced SCCs inhibited by GW627368X indicate the EP4 receptor subtype as the major mediator of PGE(2)-induced electrogenic ion secretion with a lesser induction through the EP2 receptor subtype.