Effects of prostaglandin F2αon small intestinal interstitial cells of Cajal

Abstract

To explore the role of prostaglandin F(2α) (PGF(2α))) on pacemaker activity in interstitial cells of Cajal (ICC) from mouse small intestine. In this study, effects of PGF(2α) in the cultured ICC cells were investigated with patch clamp technology combined with Ca(2+) image analysis. 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. 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.