title: Activating of ATP-dependent K+ channels comprised of K(ir) 6.2 and SUR 2B by PGE2 through EP2 receptor in cultured interstitial cells of Cajal from murine small intestine.
abstract: The interstitial cells of Cajal (ICC) are pacemaker cells in gastrointestinal tract and generate an electrical rhythm in gastrointestinal muscles. We investigated the possibility that PGE(2) might affect the electrical properties of cultured ICC by activating ATP-dependent K(+) channels and, the EP receptor subtypes and the subunits of ATP-dependent K(+) channels involved in these activities were identified. In addition, the regulation of intracellular Ca(2+) ([Ca(2+)](i)) mobilization may be involved the action of PGE(2) on ICC. Treatments of ICC with PGE(2) inhibited electrical pacemaker activities in the same manner as pinacidil, an ATP-dependent K(+) channel opener and PGE(2) had only a dose-dependent effect. Using RT-PCR technique, we found that ATP-dependent K(+) channels exist in ICC and that these are composed of K(ir) 6.2 and SUR 2B subunits. To characterize the specific membrane EP receptor subtypes in ICC, EP receptor agonists and RT-PCR were used: Butaprost (an EP(2) receptor agonist) showed the actions on pacemaker currents in the same manner as PGE(2). However sulprostone (a mixed EP(1) and EP(3) agonist) had no effects. In addition, RT-PCR results indicated the presence of the EP(2) receptor in ICC. To investigate cAMP involvement in the effects of PGE(2) on ICCs, SQ-22536 (an inhibitor of adenylate cyclase) and cAMP assays were used. SQ-22536 did not affect the effect of PGE(2) on pacemaker currents, and PGE(2) did not stimulate cAMP production. Also, we found PGE(2) inhibited the spontaneous [Ca(2+)](i) oscillations in cultured ICC. These observations indicate that PGE(2) alters pacemaker currents by activating the ATP-dependent K(+) channels comprised of K(ir) 6.2-SUR 2B in ICC and this action of PGE(2) are through EP(2) receptor subtype and also the activation of ATP-dependent K(+) channels involves intracellular Ca(2+) mobilization.
authors.affiliation: Department of Physiology, College of Medicine, Chosun University, 375 Seosuk-dong, Gwangju, South Korea.
authors.forename: Seok
authors.initials: S
authors.lastname: Choi
authors.forename: Cheol Ho
authors.initials: CH
authors.lastname: Yeum
authors.forename: In Youb
authors.initials: IY
authors.lastname: Chang
authors.forename: Ho Jin
authors.initials: HJ
authors.lastname: You
authors.forename: Jong Sung
authors.initials: JS
authors.lastname: Park
authors.forename: Han Seong
authors.initials: HS
authors.lastname: Jeong
authors.forename: Insuk
authors.initials: I
authors.lastname: So
authors.forename: Ki Whan
authors.initials: KW
authors.lastname: Kim
authors.forename: Jae Yeoul
authors.initials: JY
authors.lastname: Jun
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000819:agonists* / Q000032:analysis / Q000235:genetics; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000067956:Adenylyl Cyclase Inhibitors; D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005260:Female; D007421:Intestine, Small / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D008807:Mice, Inbred BALB C; D015221:Potassium Channels / Q000819:agonists* / Q000032:analysis / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying / Q000819:agonists* / Q000032:analysis / Q000235:genetics; D011955:Receptors, Drug / Q000819:agonists* / Q000032:analysis / Q000235:genetics; D018078:Receptors, Prostaglandin E / Q000378:metabolism*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel
chemical_list: D018528:ATP-Binding Cassette Transporters; D000225:Adenine; D000255:Adenosine Triphosphate; D000067956:Adenylyl Cyclase Inhibitors; D000527:Alprostadil; D002118:Calcium; D015232:Dinoprostone; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C545645:Ptger2 protein, mouse; C017759:9-(tetrahydro-2-furyl)-adenine; C048491:butaprost