Original Article
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World J Gastroenterol. Mar 7, 2011; 17(9): 1143-1151
Published online Mar 7, 2011. doi: 10.3748/wjg.v17.i9.1143
Effects of prostaglandin F2α on small intestinal interstitial cells of Cajal
Chan Guk Park, Young Dae Kim, Man Yoo Kim, Jae Woong Koh, Jae Yeoul Jun, Cheol Ho Yeum, Insuk So, Seok Choi
Chan Guk Park, Young Dae Kim, Man Yoo Kim, Department of Internal Medicine, College of Medicine, Chosun University, Gwangju 501-759, South Korea
Jae Woong Koh, Department of Ophthalmology, College of Medicine, Chosun University, 375 Seosuk-dong, Gwangju 501-759, South Korea
Jae Yeoul Jun, Cheol Ho Yeum, Seok Choi, Department of Physiology, College of Medicine, Chosun University, 375 Seosuk-dong, Gwangju 501-759, South Korea
Insuk So, Department of Physiology and Biophysics, College of Medicine, Seoul National University, Seoul 110-759, South Korea
Author contributions: Park CG and Kim YD designed research; Kim MY, Koh JW and Jun JY performed research; Choi S and Park CG wrote the paper; So I and Yeum CH contributed to the experiment analysis.
Supported by Research Fund from Chosun Hospital 2008
Correspondence to: Seok Choi, PhD, Professor, Department of Physiology, College of Medicine, Chosun University, 375 Seosuk-dong, Gwangju 501-759, South Korea. choiseok@chosun.ac.kr
Telephone: +82-62-2306413 Fax: +82-62-2324943
Received: August 20, 2010
Revised: November 11, 2010
Accepted: November 18, 2010
Published online: March 7, 2011
Abstract

AIM: To explore the role of prostaglandin F2α (PGF2α)) on pacemaker activity in interstitial cells of Cajal (ICC) from mouse small intestine.

METHODS: In this study, effects of PGF2α in the cultured ICC cells were investigated with patch clamp technology combined with Ca2+ image analysis.

RESULTS: Externally applied PGF2α (10 μmol/L) produced membrane depolarization in current-clamp mode and increased tonic inward pacemaker currents in voltage-clamp mode. The application of flufenamic acid (a non-selective cation channel inhibitor) or niflumic acid (a Cl- channel inhibitor) abolished the generation of pacemaker currents but only flufenamic acid inhibited the PGF2α-induced tonic inward currents. In addition, the tonic inward currents induced by PGF2α were not inhibited by intracellular application of 5’-[-thio]diphosphate trilithium salt. Pretreatment with Ca2+ free solution, U-73122, an active phospholipase C inhibitor, and thapsigargin, a Ca2+-ATPase inhibitor in endoplasmic reticulum, abolished the generation of pacemaker currents and suppressed the PGF2α-induced tonic inward currents. However, chelerythrine or calphostin C, protein kinase C inhibitors, did not block the PGF2α-induced effects on pacemaker currents. When recording intracellular Ca2+ ([Ca2+]i) concentration using fluo-3/AM, PGF2α broadly increased the spontaneous [Ca2+]i oscillations.

CONCLUSION: These results suggest that PGF2α can modulate pacemaker activity of ICC by acting non-selective action channels through phospholipase C-dependent pathway via [Ca2+]i regulation

Keywords: Prostaglandin F2α; Interstitial cells of Cajal; Tonic inward currents; Intestinal motility