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Bradykinin modulates pacemaker currents through bradykinin B2 receptors in cultured interstitial cells of Cajal from the murine small intestine

Authors
Publisher
Nature Publishing Group
Publication Date
Keywords
  • Animals
  • Biological Clocks/*Drug Effects
  • Bradykinin/*Pharmacology
  • Calcium/Physiology
  • Calcium-Transporting Atpases/Antagonists & Inhibitors
  • Cells
  • Cultured
  • Chloride Channels/Antagonists & Inhibitors
  • Cyclooxygenase Inhibitors/Pharmacology
  • Enzyme Inhibitors/Pharmacology
  • Female
  • Intestine
  • Small/Cytology/Drug Effects/*Metabolism
  • Immunohistochemistry
  • Male
  • Mice
  • Mice
  • Inbred Balb C
  • Patch-Clamp Techniques
  • Protein Kinase C/Antagonists & Inhibitors
  • Receptor
  • Bradykinin B2/*Drug Effects
  • Signal Transduction/Drug Effects
  • Sodium/Physiology
Disciplines
  • Biology

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.

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