Effects of prostaglandin F2αon small intestinal interstitial cells of Cajal

AIM: To explore the role of prostaglandin F(2α) (PGF(2α))) on pacemaker activity in interstitial cells of Cajal (ICC) from mouse small intestine. METHODS: In this study, effects of PGF(2α) in the cultured ICC cells were investigated with patch clamp technology combined with Ca(2+) image analysis. RESULTS: Externally applied PGF(2α) (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 PGF(2α)-induced tonic inward currents. In addition, the tonic inward currents induced by PGF(2α) were not inhibited by intracellular application of 5'-[-thio]diphosphate trilithium salt. Pretreatment with Ca(2+) free solution, U-73122, an active phospholipase C inhibitor, and thapsigargin, a Ca(2+)-ATPase inhibitor in endoplasmic reticulum, abolished the generation of pacemaker currents and suppressed the PGF(2α)-induced tonic inward currents. However, chelerythrine or calphostin C, protein kinase C inhibitors, did not block the PGF(2α)-induced effects on pacemaker currents. When recording intracellular Ca(2+) ([Ca(2+)](i)) concentration using fluo-3/AM, PGF(2α) broadly increased the spontaneous [Ca(2+)](i) oscillations. CONCLUSION: These results suggest that PGF(2α) can modulate pacemaker activity of ICC by acting non-selective action channels through phospholipase C-dependent pathway via [Ca(2+)]i regulation.