Bradykinin modulates pacemaker currents through bradykinin B2 receptors in cultured interstitial cells of Cajal from the murine small intestine.
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.
Choi
Seok
S
Department of Physiology, College of Medicine, Chosun University, 375 Seosuk-Dong, Gwangju 501-759, Korea.
Park
Do Young
DY
Yeum
Cheol Ho
CH
Chang
In Youb
IY
You
Ho Jin
HJ
Park
Chan Guk
CG
Kim
Man Yoo
MY
Kong
In Deok
ID
So
Insuk
I
Kim
Ki Whan
KW
Jun
Jae Yeoul
JY
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
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