Effects of pine needle extract on pacemaker currents in interstitial cells of Cajal from the murine small intestine.
Extracts of pine needles (Pinus densiflora Sieb. et Zucc.) have diverse physiological and pharmacological actions. In this study we show that pine needle extract alters pacemaker currents in interstitial cells of Cajal (ICC) by modulating ATP-sensitive K+ channels and that this effect is mediated by prostaglandins. In whole cell patches at 30 degrees , ICC generated spontaneous pacemaker potentials in the current clamp mode (I = 0), and inward currents (pacemaker currents) in the voltage clamp mode at a holding potential of -70 mV. Pine needle extract hyperpolarized the membrane potential, and in voltage clamp mode decreased both the frequency and amplitude of the pacemaker currents, and increased the resting currents in the outward direction. It also inhibited the pacemaker currents in a dose-dependent manner. Because the effects of pine needle extract on pacemaker currents were the same as those of pinacidil (an ATP-sensitive K+ channel opener) we tested the effect of glibenclamide (an ATP-sensitive K+ channels blocker) on ICC exposed to pine needle extract. The effects of pine needle extract on pacemaker currents were blocked by glibenclamide. To see whether production of prostaglandins (PGs) is involved in the inhibitory effect of pine needle extract on pacemaker currents, we tested the effects of naproxen, a non-selective cyclooxygenase (COX-1 and COX-2) inhibitor, and AH6809, a prostaglandin EP1 and EP2 receptor antagonist. Naproxen and AH6809 blocked the inhibitory effects of pine needle extract on ICC. These results indicate that pine needle extract inhibits the pacemaker currents of ICC by activating ATP-sensitive K+ channels via the production of PGs.
Cheong
Hyeonsook
H
Department of Physiology, College of Medicine, Chosun University, Gwangju 501-759, Korea.
Paudyal
Dilli Parasad
DP
Jun
Jae Yeoul
JY
Yeum
Cheol Ho
CH
Yoon
Pyung Jin
PJ
Park
Chan Guk
CG
Kim
Man Yoo
MY
So
Insuk
I
Kim
Ki Whan
KW
Choi
Seok
S
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005905:Glyburide / Q000494:pharmacology; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009288:Naproxen / Q000494:pharmacology; D020110:Pinacidil / Q000494:pharmacology; D028223:Pinus / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011453:Prostaglandins / Q000096:biosynthesis / Q000502:physiology
D010936:Plant Extracts; D015221:Potassium Channels; D011453:Prostaglandins; D009288:Naproxen; D020110:Pinacidil; D000255:Adenosine Triphosphate; D005905:Glyburide