The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Effects of Lubiprostone on Pacemaker Activity of Interstitial Cells of Cajal from the Mouse Colon

  • Jiao, Han-Yi (Department of Physiology, College of Medicine, Chosun University) ;
  • Kim, Dong Hyun (Department of Radiology, College of Medicine, Chosun University) ;
  • Ki, Jung Suk (Department of Physiology, College of Medicine, Chosun University) ;
  • Ryu, Kwon Ho (Department of Physiology, College of Medicine, Chosun University) ;
  • Choi, Seok (Department of Physiology, College of Medicine, Chosun University) ;
  • Jun, Jae Yeoul (Department of Physiology, College of Medicine, Chosun University)
  • Received : 2014.05.01
  • Accepted : 2014.07.09
  • Published : 2014.08.30
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Abstract

Lubiprostone is a chloride ($Cl^-$) channel activator derived from prostaglandin $E_1$ and used for managing constipation. In addition, lubiprostone affects the activity of gastrointestinal smooth muscles. Interstitial cells of Cajal (ICCs) are pacemaker cells that generate slow-wave activity in smooth muscles. We studied the effects of lubiprostone on the pacemaker potentials of colonic ICCs. We used the whole-cell patch-clamp technique to determine the pacemaker activity in cultured colonic ICCs obtained from mice. Lubiprostone hyperpolarized the membrane and inhibited the generation of pacemaker potentials. Prostanoid $EP_1$, $EP_2$, $EP_3$, and $EP_4$ antagonists (SC-19220, PF-04418948, 6-methoxypyridine-2-boronc acid N-phenyldiethanolamine ester, and GW627368, respectively) did not block the response to lubiprostone. L-NG-nitroarginine methyl ester (L-NAME, an inhibitor of nitric oxide synthase) and 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) did not block the response to lubiprostone. In addition, tetraethylammonium (TEA, a voltage-dependent potassium [$K^+$] channel blocker) and apamin (a calcium [$Ca^{2+}$]-dependent $K^+$ channel blocker) did not block the response to lubiprostone. However, glibenclamide (an ATP-sensitive $K^+$ channel blocker) blocked the response to lubiprostone. Similar to lubiprostone, pinacidil (an opener of ATP-sensitive $K^+$ channel) hyperpolarized the membrane and inhibited the generation of pacemaker potentials, and these effects were inhibited by glibenclamide. These results suggest that lubiprostone can modulate the pacemaker potentials of colonic ICCs via activation of ATP-sensitive $K^+$ channel through a prostanoid EP receptor-independent mechanism.

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References

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