Effects of Cyclobuxine E on Two Distinct Types of Potassium-Activated Calcium Channels in an Intestinal Smooth Muscle

흰쥐 장관에 있어 칼륨에 의해 활성화되는 칼슘 채널에 대한 Cyclobuxine E의 영향

  • Lee, Jong-Hwoa (Department of Pharmacology, College of Medicine, Soonchunhyang University) ;
  • Kwon, Jun-Tack (Department of Pharmacology, College of Medicine, Soonchunhyang University) ;
  • Cho, Byung-Heon (Department of Pharmacology, College of Medicine, Soonchunhyang University) ;
  • Choi, Kyu-Hong (Department of Pharmacology, College of Medicine, Soonchunhyang University) ;
  • Kim, Yu-Jae (Department of Pharmacology, College of Medicine, Soonchunhyang University) ;
  • Kim, Jong-Bae (Department of Pharmacology, College of Medicine, Soonchunhyang University) ;
  • Kim, Chun-Sook (Department of Pharmacology, College of Medicine, Soonchunhyang University) ;
  • Cha, Young-Deog (Department of Pharmacology, College of Medicine, Soonchunhyang University) ;
  • Kim, Young-Suk (Department of Pharmacology, College of Medicine, Soonchunhyang University)
  • 이종화 (순천향대학 의학부 약리학교실) ;
  • 권준택 (순천향대학 의학부 약리학교실) ;
  • 조병헌 (순천향대학 의학부 약리학교실) ;
  • 최규홍 (순천향대학 의학부 약리학교실) ;
  • 김유재 (순천향대학 의학부 약리학교실) ;
  • 김종배 (순천향대학 의학부 약리학교실) ;
  • 김천숙 (순천향대학 의학부 약리학교실) ;
  • 차영덕 (순천향대학 의학부 약리학교실) ;
  • 김영석 (순천향대학 의학부 약리학교실)
  • Published : 1989.06.30

Abstract

For several years, we investigated the pharmacological action of several substances isolated from Buxus microphylla var koreana Nakai, which had been used as folk remedies of malaria and venereal disease. Cyclobuxine $D(C_{25}H_{42}ON_2)$, a steroidal alkaloid, exerted an antiinflammatory action, hypotensive and bradycardic effects in rats. In the present study, we isolated alkaloid from the acetone-insoluble fraction of the strong bases of this plants. This alkaloid $(C_{25}H_{38}ON_2)$ was identified as a steroidal alkaloid contained a cyclopropane ring by physical and chemical methods. It is a derivative of cyclobuxine D and named cyclobuxine E. We examined the effect of cyclobuxine E on the contractile response induced by acetylcholine and two distinct types of potassium-activated calcium channels in an intestinal smooth muscle of the rat. Cyclobuxine E inhibited significantly the Ach-induced contraction. The isolated longitudinal muscle from the rat duodenum was immersed calcium-depleted potassium depolarizing solution. Ten minutes after, 1.8 mM $CaCl_2$ was added to muscle bath and elicited a biphasic increase in muscle tension. Cyclobuxine E produced an appreciable inhibition of both components of the mechanical response. In addition, Cyclobuxine E introduced at a point when the tonic response had reached its maximum level, caused the muscle to exhibit a rapid loss of tension. Based on these experimental results, we proposed the possibility that the inhibitory action of cyclobuxine E on the isolated rat duodenum may be due to inhibiting the transmembrane fluxes of calcium ion in potassium-activated calcium channels.

본 연구실에는 최근 수년동안 말라리아, 성병등에 민간약으로 사용되어 온 회양목(Buxus microphylla var. koreana Nakai)으로 부터 다수의 물질을 분리하여 그 약리작용을 경색하여왔다. Coumarin의 유도체인 buxuletin은 이뇨 작용이 있음이 인정되었으며, steroid 성 alkaloid인 Cyclobuxine $D(C_{25}H_{42}ON_2)$는 항염증작용, 흰쥐에서 심박동수 감소작용 및 적출 평활근 이완 작용을 나타냈다. 본 연구에서는 회양목에서 Cyclobuxine D의 유도체인 Cyclobuxine $E(C_{24}H_{38}ON_2)$를 분리하여 그 구조를 이화학적인 방법으로 규명하였으며 흰쥐의 십이지장 평활근에서 acetylcholine에 의해 유도되는 수축 작용에 대한 영향과 높은 칼륨 이온에 의해 활성화되는 칼슘 채널에 대한 Cyclobuxine E의 영향을 관찰하였다. Cyclobuxine E는 적출 십이지장 평활근에서 acetylcholine의 수축작용을 현저히 억제하였으며, Calcium-depleted potassium-depolarizing 용액에 담근 후 $CaCl_2$를 가함으로써 나타나는 이중적인 수축작용을 용량적으로 차단하였다. 이상의 십이지장 평활근에 대한 Cyclobuxine E의 작용은 Cyclobuxine E가 칼륨에 의해 활성화되는 칼슘 채널 (아마, voltage-dependent calcium channel)을 통한 칼슘의 세포막 통과를 차단하므로 인해 나타남을 시사한다.

Keywords