title: Bradykinin modulates pacemaker currents through bradykinin B2 receptors in cultured interstitial cells of Cajal from the murine small intestine.
abstract: We studied the modulation of pacemaker activities by bradykinin in cultured interstitial cells of Cajal (ICC) from murine small intestine with the whole-cell patch-clamp technique. Externally applied bradykinin produced membrane depolarization in the current-clamp mode and increased tonic inward pacemaker currents in the voltage-clamp mode. Pretreatment with bradykinin B1 antagonist did not block the bradykinin-induced effects on pacemaker currents. However, pretreatment with bradykinin B2 antagonist selectively blocked the bradykinin-induced effects. Also, only externally applied selective bradykinin B2 receptor agonist produced tonic inward pacemaker currents and ICC revealed a colocalization of the bradykinin B2 receptor and c-kit immunoreactivities, but bradykinin B1 receptors did not localize in ICC. External Na(+)-free solution abolished the generation of pacemaker currents and inhibited the bradykinin-induced tonic inward current. However, a Cl(-) channel blocker (DIDS) did not block the bradykinin-induced tonic inward current. The pretreatment with Ca(2+)-free solution and thapsigargin, a Ca(2+)-ATPase inhibitor in endoplasmic reticulum, abolished the generation of pacemaker currents and suppressed the bradykinin-induced action. Chelerythrine and calphostin C, protein kinase C inhibitors or naproxen, an inhibitor of cyclooxygenase, did not block the bradykinin-induced effects on pacemaker currents. These results suggest that bradykinin modulates the pacemaker activities through bradykinin B2 receptor activation in ICC by external Ca(2+) influx and internal Ca(2+) release via protein kinase C- or cyclooxygenase-independent mechanism. Therefore, the ICC are targets for bradykinin and their interaction can affect intestinal motility.
authors.affiliation: Department of Physiology, College of Medicine, Chosun University, 375 Seosuk-Dong, Gwangju 501-759, Korea.
authors.forename: Seok
authors.initials: S
authors.lastname: Choi
authors.forename: Do Young
authors.initials: DY
authors.lastname: Park
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: Chan Guk
authors.initials: CG
authors.lastname: Park
authors.forename: Man Yoo
authors.initials: MY
authors.lastname: Kim
authors.forename: In Deok
authors.initials: ID
authors.lastname: Kong
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: D000818:Animals; D001683:Biological Clocks / Q000187:drug effects*; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D043782:Receptor, Bradykinin B2 / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D012964:Sodium / Q000502:physiology
chemical_list: D018118:Chloride Channels; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D043782:Receptor, Bradykinin B2; D012964:Sodium; D011493:Protein Kinase C; D000252:Calcium-Transporting ATPases; D001920:Bradykinin; D002118:Calcium