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Inhibition of Intestinal Motility by the Putative $BK_{Ca}$ Channel Opener LDD175
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  • Inhibition of Intestinal Motility by the Putative $BK_{Ca}$ Channel Opener LDD175
저자명
Pena. Ike Campomayor Dela,Yoon. Seo-Young,Kim. Sung-Mok,Lee. Geum-Seon,Park. Chul-Seung,Kim. Yong-Chul,Cheong. Jae-Hoon
간행물명
Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea
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2009년|32권 3호|pp.413-420 (8 pages)
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
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기타언어초록

LDD175 (4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid) is a benzofuroindole compound characterized previously as a potent opener of the large conductance calcium activated ($BK_{Ca}$) channels. Activators of the $BK_{Ca}$ channels are potential therapies for smooth muscle hyperactivity disorders. The present study investigates the influence of LDD175 on the mechanical activity of the ileum smooth muscle. LDD175 inhibited spontaneous contractions of the ileum in a concentration-dependent manner ($pEC_{50}=5.9;{pm};0.1$) ($E_{max}=96;{pm};1.0%$ at $100;{mu}M$, n=3). It also remarkably inhibited contractions due to acetylcholine (ACh) ($pEC_{50}=5.3;{pm};0.1$)($E_{max}=97.7;{pm};2.3%$, n=6) and electrical field stimulation (EFS) ($pEC_{50}=5.5;{pm};0.1$) ($E_{max}=83.3;{pm};6.0%$, n=6). In strips precontracted by 20 mM KCl, LDD175 significantly reduced the contractions yielding a $pEC_{50}$ of $6.1;{pm};0.1$ and $E_{max}$ of $96.6;{pm};0.9%$, (n=6). In 60 mM KCl, a concentration-dependent inhibition was observed with respective $pEC_{50}$ and $E_{max}$ values of $4.1;{pm};0.1$ and $50.8;{pm};5.0%$ (n=3). $BK_{Ca}$ channel blockers iberiotoxin (IbTX) and tetraethylammonium chloride (TEA, 1 mM) attenuated the relaxative effect of LDD175 but not barium chloride ($BaCl_2$), and glibenclamide ($K_{IR}$ and $K_{ATP}$ channel blockers, respectively). These data demonstrate the antispasmodic activity of LDD175 attributable to the potentiation of the $BK_{Ca}$channels.