Inhibitory effects of potassium channel openers on the oxytocin-induced contraction of the rat uterus in vitro

H. J. Kim, M. H. Lee, P. D. Ryu

Research output: Contribution to journalArticlepeer-review

Abstract

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 pencreatic β-cell. In the present study, we investgated 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 10 μM) 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 apemin. Contractions induced by low concentration of KCl (< 40 mM) were inhibited by cromakalim (100 μM) and nicorandil (300 μM) but those evoked by higher concentration (< 40 mM) of KCl were little affected. In ovariectomized rat uterus, cromakalim dose-dependently inhibited oxytocin-induced contraction and glibenclamide (10 μM) inhibited the relaxant effect of cromakalim with pD2 and K(B) values of 7.48 and 1.26 x 10-7 M, respectively. In estrogen-primed rat uterus, these values were 6.51 and 1.57 x 10-7 M, 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+ channel which is blocked by glibenclamide.

Original languageEnglish (US)
Pages (from-to)191-203
Number of pages13
JournalKorean Journal of Pharmacology
Volume30
Issue number2
StatePublished - 1994

Keywords

  • cromakalim
  • glibenclamide
  • nicorandil
  • potassium channel opener
  • rat uterus

ASJC Scopus subject areas

  • Pharmacology

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