The Effect of Potassium Channel Opener Pinacidil on the Non‐Pregnant Rat Uterus

Aug 19, 2007Basic & clinical pharmacology & toxicology

Effects of the potassium channel opener pinacidil on the uterus of non-pregnant rats

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Abstract

Pinacidil produced more potent inhibition of oxytocin-elicited contractions in the isolated uterus of non-pregnant rats.

Pinacidil inhibited oxytocin-induced contractions more effectively than spontaneous rhythmic contractions or those induced by electrical stimulation.
The selective blocker glibenclamide antagonized the inhibition of oxytocin-elicited contractions by pinacidil in a competitive manner.
Inhibition of spontaneous rhythmic contractions and contractions from electrical stimulation by pinacidil was antagonized non-competitively by glibenclamide.
Pinacidil completely relaxed uterine strips pre-contracted with a potassium-rich solution, indicating a potential K(+) channel-independent mechanism.
Further investigation is needed to understand the differing interactions between glibenclamide and pinacidil based on contraction type.

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The effects of the K(+) channel opener, pinacidil on the spontaneous rhythmic contractions and contractions provoked by electrical field stimulation (50 Hz) or by oxytocin were investigated in the isolated uterus of the non-pregnant rat in oestrus. Pinacidil produced more potent inhibition of oxytocin-elicited contractions than of spontaneous rhythmic contractions or electrical field stimulation-induced contractions. Glibenclamide, a selective blocker of adenosine triphosphate (ATP)-sensitive K(+) (K(ATP)) channels, antagonized the pinacidil-induced inhibition of contractions elicited by oxytocin in a competitive manner. However, the pinacidil-induced inhibition of electrical field stimulation-elicited contractions and spontaneous rhythmic contractions was antagonized non-competitively by glibenclamide. In the uterine strips pre-contracted with 80 mM K(+), the pinacidil-induced maximal relaxation was not affected. The present data show that pinacidil exhibits potent relaxant properties in the rat non-pregnant uterus in oestrus and therefore should be taken into account as a possible agent for treatment of dysmenorrhoea. Based on glibenclamide affinity, it appears that the inhibitory response to pinacidil involves K(ATP )channels. We need further investigations to explain why the interaction between glibenclamide and pinacidil in this experimental model depends on the nature of contractions. The ability of pinacidil to completely relax the rat non-pregnant uterus pre-contracted with K(+)-rich solution suggests that K(+) channel-independent mechanism(s) also play a part in its relaxant effect.

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The Effect of Potassium Channel Opener Pinacidil on the Non‐Pregnant Rat Uterus

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