Mosa Ahmed Soliman, Hansen Mark Berner, Tilotta Cristina Maria, Bindslev Niels
Department of Gastrointestinal Surgery K, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
Basic Clin Pharmacol Toxicol. 2008 Sep;103(3):214-21. doi: 10.1111/j.1742-7843.2008.00257.x. Epub 2008 Jul 18.
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 (EP(2)), sulprostone (EP(1) and EP(3)) and PGE(1) alcohol (OH-PGE(1)) (EP(4)). GW627368X was used as a specific EP(4) receptor antagonist. Forskolin-induced SCC was used as a control of tissue viability. The mean basal SCC was 24.5 +/- 0.9 microA/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 microA/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 microM, 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 EP(4) receptor subtype as the major mediator of PGE(2)-induced electrogenic ion secretion with a lesser induction through the EP(2) receptor subtype.
本研究旨在确定在大鼠结肠中参与电生性离子分泌的前列腺素EP受体亚型。使用30只大鼠，通过尤斯灌流小室技术测量短路电流（SCC）和斜率电导。将前列腺素E2（PGE(2)）和其他EP受体选择性激动剂应用于用吲哚美辛和茶碱预处理的大鼠结肠条。受体特异性激动剂为布他前列素（EP(2)）、舒前列素（EP(1)和EP(3)）以及PGE(1)醇（OH-PGE(1)）（EP(4)）。GW627368X用作特异性EP(4)受体拮抗剂。 Forskolin诱导的SCC用作组织活力的对照。平均基础SCC为24.5±0.9微安/平方厘米（范围9.8 - 45.1），平均基础斜率电导为23.7±6.1毫西门子/平方厘米（范围9.7 - 39.8）。吲哚美辛预处理后基础SCC降低，茶碱预处理后基础SCC升高。PGE(2)、布他前列素和OH-PGE(1)刺激SCC最大增加（分别为55.8±4.1、43.9±3.8和93.9±2.7微安/平方厘米），而舒前列素无明显作用。GW627368X消除了OH-PGE(1)诱导的SCC并部分消除了PGE(2)诱导的SCC，而布他前列素诱导的SCC几乎未受影响。20微摩尔的布美他尼抑制了40%至80%的激动剂诱导的SCC变化。总之，EP受体亚型特异性受体激动剂诱导SCC的结果以及GW627368X抑制诱导SCC的模式表明，EP(4)受体亚型是PGE(2)诱导的电生性离子分泌的主要介质，通过EP(2)受体亚型的诱导作用较小。
