The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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[$PGE_2$ Regulates Pacemaker Currents through $EP_2-Receptor$ in Cultured Interstitial Cells of Cajal from Murine Small Intestine

  • Choi, Seok (Department of Physiology, College of Medicine, Chosun University) ;
  • Cho, Kyung-Won (Department of Physiology, College of Medicine, Chosun University) ;
  • Reu, Jong-Hyun (Department of Physiology, College of Medicine, Chosun University) ;
  • Kim, Jun-Soo (Department of Physiology, College of Medicine, Chosun University) ;
  • Mun, Hyun-Sik (Department of Physiology, College of Medicine, Chosun University) ;
  • Kim, Myung-Young (Department of Physiology, College of Medicine, Chosun University) ;
  • Park, Kwang-Chul (Department of Physiology, College of Medicine, Chosun University) ;
  • Heo, Gwang-Sik (Department of Physiology, College of Medicine, Chosun University) ;
  • Chang, Sung-Jong (Department of Physiology, College of Medicine, Chosun University) ;
  • Yeum, Cheol-Ho (Department of Physiology, College of Medicine, Chosun University) ;
  • Yoon, Pyung-Jin (Department of Physiology, College of Medicine, Chosun University) ;
  • Jun, Jae-Yeoul (Department of Physiology, College of Medicine, Chosun University)
  • Published : 2004.06.21
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Abstract

The interstitial cells of Cajal (ICCs) are the pacemaker cells in gastrointestinal tract and generate electrical rhythmicity in gastrointestinal muscles. Therefore, ICC may be modulated by endogenous agents such as neurotransmitter, hormones, and prostaglandins (PGs). In the present study, we investigated the effects of prostaglandins, especially $PGE_2$, on pacemaker currents in cultured ICCs from murine small intestine by using whole-cell patch clamp techniques. ICCs generated spontaneous slow waves under voltage-clamp conditions and showed a mean amplitude of $-452{\pm}39\;pA$ and frequency of $18{\pm}2$ cycles/min (n=6). Treatments of the cells with $PGE_2$ $(1\;{\mu}M)$ decreased both the frequency and amplitude of the pacemaker currents and increased the resting currents in the outward direction. $PGE_2$ had only inhibitory effects on pacemaker currents and this inhibitory effect was dose-dependent. For characterization of specific membrane EP receptor subtypes, involved in the effects of $PGE_2$ on pacemaker currents in ICCs, EP receptor agonists were used: Butaprost $(1\;{\mu}M)$, $EP_2$ receptor agonist, reduced the spontaneous inward current frequency and amplitude in cultured ICCs (n=5). However sulprostone $(1\;{\mu}M)$, a mixed $EP_1$ and $EP_3$ agonist, had no effects on the frequency, amplitude and resting currents of pacemaker currents (n=5). SQ-22536 (an inhibitor of adenylate cyclase; $100\;{\mu}M$) and ODQ (an inhibitor of guanylate cyclase; $100\;{\mu}M$) had no effects on $PGE_2$ actions of pacemaker currents. These observations indicate that $PGE_2$ alter directly the pacemaker currents in ICCs, and that the $PGE_2$ receptor subtypes involved are the $EP_2$ receptor, independent of cyclic AMP- and GMP-dependent pathway.

Keywords

References

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