Deoxycholic acid inhibits pacemaker currents by activating ATP-dependent K+ channels through prostaglandin E2 in interstitial cells of Cajal from the murine small intestine.
1. We investigated the role of deoxycholic acid in pacemaker currents using whole-cell patch-clamp techniques at 30 degrees C in cultured interstitial cells of Cajal (ICC) from murine small intestine. 2. The treatment of ICC with deoxycholic acid resulted in a decrease in the frequency and amplitude of pacemaker currents and increases in resting outward currents. Also, under current clamping, deoxycholic acid produced the hyperpolarization of membrane potential and decreased the amplitude of the pacemaker potentials. 3. These observed effects of deoxycholic acid on pacemaker currents and pacemaker potentials were completely suppressed by glibenclamide, an ATP-sensitive K(+) channel blocker. 4. NS-398, a specific cyclooxygenase-2 (COX-2) inhibitor, significantly inhibited the deoxycholic acid-induced effects. The treatment with prostaglandin E(2) (PGE(2)) led to a decrease in the amplitude and frequency of pacemaker currents and to an increase in resting outward currents, and these observed effects of PGE(2) were blocked by glibenclamide. 5. We next examined the role of deoxycholic acid in the production of PGE(2) in ICC, and found that deoxycholic acid increased PGE(2) production through the induction of COX-2 enzyme activity and its gene expression. 6. The results suggest that deoxycholic acid inhibits the pacemaker currents of ICC by activating ATP-sensitive K(+) channels through the production of PGE(2).
Jun
Jae Yeoul
JY
Department of Physiology, College of Medicine, Chosun University, 375 Seosuk-dong, Gwangju 501-759, Korea.
Choi
Seok
S
Chang
In-Youb
IY
Yoon
Cha Kyung
CK
Jeong
Hye-Gwang
HG
Kong
In Deok
ID
So
Insuk
I
Kim
Ki Whan
KW
You
Ho Jin
HJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003840:Deoxycholic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D003840:Deoxycholic Acid; D000255:Adenosine Triphosphate; D015232:Dinoprostone; D005905:Glyburide