쥐자궁근의 운동성에 대한 K+채널 개방제의 이완 작용

• 영문명: Inhibitory Effects of Potassium Channel Openers on the Oxytocin-induced Contraction of the Rat Uterus in vitro
• 발행기관: 대한약리학회
• 저자명: 김희정(Hee Jeong Kim) 이문한(Mun Han Lee) 류판동(Pan Dong Ryu)
• 간행물 정보: 『대한약리학잡지』제30권 제2호, 191~204쪽, 전체 14쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 1994.09.30

영문 초록

K⁺ channel openers (KCOs) are known to have a wide range of effects by opening the K⁺ channel in plasma membranes of various smooth muscles, cardiac muscle and pancreatic β-cell. In the present study, we investigated the effects of 5 types of KCOs, cromakalim, RP49356, pinacidil, nicorandil and diazoxide on the contractility of isolated rat uterus. All KCOs tested inhibited the uterine contraction induced by 0.2 nM oxytocin in a dose-dependent manner. Individual KCO and its pD₂ values were cromakalim 6.5, RP49356 6.3, pinacidil 5.92, nicorandil 4.43 and diazoxide 4.18. The relaxant effects of KCO were inhibited by glibenclamide (0.3, 1 and 10μM) with pA₂ values of cromakalim 6.91, RP49356 6.59, pinacidil 6.55, nicorandil 5.97 and diazoxide 6.37. In addition, the relaxant effect of cromakalim or pinacidil was antagonised by TEA, a non-selective K⁺ channel blocker, but not by apamin. Contractions induced by low concentration of KCI (< 40 mM) were inhibited by cromakalim (100μM) and nicorandil (300μM), but those evoked by higher concentration (> 40 mM) of KCI were little affected. In ovariectomized rat uterus, cromakalim dose-dependently inhibited oxytocin-induced contraction and glibenclamide (10μM) inhibited the relaxant effect of cromakalim with pD₂ and K_B values of 7.48 and 1.26 × 10^-7M, respectively. In estrogen-primed rat uterus, these values were 6.51 and 1.57 × 10^-7M, respectively, indicating that the cromakalim is less effective on the estrogen-treated uterine smooth muscle. Our results suggest that the KCO-sensitive K⁺ channels participate in the motility of uterine smooth muscle and such channels are, at least in part, under the control of estrogen. In addition, our data Indicate that the type of K⁺ channels activated by KCO is ATP-sensitive K⁺ channels which is blocked by glibenclamide.

키워드

Potassium channel opener Cromakalim Nicorandil Rat uterus Glibenclamide