Effects of several potassium channel openers and glibenclamide on the uterus of the rat

Piper, I.; Minshall, Eleanor; Downing, Sandra J.; Hollingsworth, Michael A.; Sadraei, Hassan

doi:10.1111/j.1476-5381.1990.tb14178.x

Cited by 56 publications

(43 citation statements)

References 21 publications

(37 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Effect of glibenclamide on 86Rb efflux and contractions in cyanide A variety of K+ channels have been described in the uterus (Toro, Stefani & Erulkar 1990) (Standen, Quayle, Davies, Brayden, Huang & Nelson, 1989;Piper, Minshall, Downing, Hollingsworth & Sadraei, 1990). The effects of glibenclamide (20 #M) on the rate constant of 86Rb efflux in cyanide were therefore examined.…”

Section: Resultsmentioning

confidence: 99%

Effects of metabolic inhibition and changes of intracellular pH on potassium permeability and contraction of rat uterus.

Heaton

Wray

Eisner

1993

The Journal of Physiology

View full text Add to dashboard Cite

SUMMARY1. We have investigated the role of changes of potassium efflux in the inhibition of uterine force produced by cyanide. K+ efflux (86Rb) was measured from pregnant and non-pregnant rat myometrial strips during metabolic inhibition with cyanide and following manoeuvres to displace intracellular pH (pHi).2. Cyanide greatly reduced or abolished spontaneous contractions. If the membrane was depolarized directly at this stage (by elevating external K+) then contraction redeveloped. This suggests that the initial depression of force is due to a failure of membrane excitation.3. Cyanide reversibly increased 86Rb efflux (30-35%) in both pregnant and nonpregnant uteri and contraction was reduced. The increase in 86Rb efflux with cyanide was not secondary to changes of membrane potential as it also occurred in both high-K+ and Ca2+-free solutions. 6. Intracellular alkalinization produced by the weak base trimethylamine (60 mM) increased the frequency of uterine contraction and the 86Rb efflux. However, there was no effect on the 86Rb efflux in a Ca2+-free solution. The increased efflux is therefore presumably a consequence of the increased frequency.7. It is concluded that metabolic inhibition produced by cyanide, produces an increase in K+ efflux from the myometrium. Part of this efflux is glibenclamide sensitive. This increased K+ efflux will lead to hyperpolarization of the myometrial membrane and thus decrease excitation. Thus reduced surface membrane excitability will contribute to the fall of force in hypoxia; specifically it may cause the initial loss of spontaneous contractions in the uterus.MS 1322

show abstract

Section: Resultsmentioning

confidence: 99%

Effects of metabolic inhibition and changes of intracellular pH on potassium permeability and contraction of rat uterus.

Heaton

Wray

Eisner

1993

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…ATP-dependent K+ channels (Sturgess et al, 1988;Escande et al, 1989;Standen et al, 1989) has been used in vivo to demonstrate antagonism of the hypotensive and uterine-relaxant actions of the K+-channel opener cromakalim (Buckingham et al, 1989;Cavero et al, 1989;Quast & Cook, 1989, Piper et al, 1990. Apamin is another highly selective blocker of K+-channels, in this case the small calcium-activated K+-channel (Weir & Weston, 1986;Cook & Hof, 1988).…”

Section: Introductionmentioning

confidence: 99%

Antagonism of relaxin by glibenclamide in the uterus of the rat in vivo

Downing

Hollingsworth

1991

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

1 The effects of glibenclamide (a blocker of adenosine triphosphate [ATP]-dependent K+-channels) on the inhibition of uterine contractions by relaxin, salbutamol and cromakalim were compared in vivo.2 Glibenclamide (20mgkg-1) did not antagonize salbutamol. Glibenclamide produced a parallel rightward shift in the dose-response curve to cromakalim with a 5.5 fold decrease in uterine sensitivity (postvehicle log ID50, -0.87mgkg'1; post-glibenclamide log ID50, -0.07mgkg-1). Glibenclamide produced a non-parallel rightward shift in the dose-response curve to relaxin (post-vehicle log ID50, 0.99 ug kg1; post-glibenclamide log ID50, 2.28 jug kg-1).3 Glibenclamide reversed established inhibition of uterine contractions by cromakalim or relaxin but not that by salbutamol. 4 Insulin produced no antagonism of relaxin on isolated uterus of the rat, demonstrating that glibenclamide antagonism of relaxin in vivo is not by released insulin. Apamin did not antagonize relaxin in vivo, suggesting that small calcium-activated K+-channels are not involved in the action of relaxin. 5 Comparison of the lack of antagonism of salbutamol with the non-competitive-like antagonism of relaxin by glibenclamide suggests that relaxin does not relax uterine smooth muscle predominantly by increasing intracellular adenosine 3', 5'-cyclic monophosphate concentrations. Comparison of the noncompetitive-like antagonism of relaxin and the competitive-like antagonism of cromakalim by glibenclamide suggests that the two relaxants may share, in part, a common mechanism of action and that additional mechanism(s) may also be involved in the inhibitory action of relaxin.

show abstract

“…Rather the response was observed with all the structurally-disparate K-channel openers tested and was elicited at concentrations similar to those which produce the relaxant responses in PSS. The rank order of potency of these agents (Ro 31-6930> cromakalim > minoxidil sulphate > pinacidil > BRL 38226) was also similar to that found for the relaxant effects of the K-channel openers in a variety of other experimental systems Newgreen et al, 1990;Paciorek et al, 1990;Piper et al, 1990). The observed low potency of BRL 38226 (the (+)-enantiomeric component of cromakalim) is consistent with previous findings that this enantiomer is the less potent relaxant and hypotensive component of cromakalim (Buckingham et al, 1986;Hof et al, 1988).…”

Section: Discussionmentioning

confidence: 63%

“…The first of these, which is a diagnostic feature of agents like cromakalim (Buckingham et al, 1989;Murray et al, 1989, Newgreen et al, 1990Piper et al, 1990) was the ability of glibenclamide, a blocker of the ATP-sensitive K-channel in cardiac myocytes (Escande et al, 1988) and pancreatic P cells (Zunkler et al, 1988), to inhibit the response. Pretreatment with this agent produced a competitive-like inhibition of the K-channel opener induced contraction to cromakalim, consistent with an association between this event and the opening of glibenclamide-sensitive K-channels.…”

Section: Discussionmentioning

confidence: 99%

Characteristics of the contractile response of rabbit aorta produced by cromakalim in calcium‐free solution

Duty

Weston

1992

British J Pharmacology

View full text Add to dashboard Cite

1 The effect of potassium channel opening compounds has been investigated in the smooth muscle of rabbit aorta under Ca-free conditions. Examination of the characteristics of the response has been performed using cromakalim as the prototype compound. 2 In order of potency, Ro 31-6930, cromakalim, minoxidil sulphate and pinacidil each produced a contraction in rabbit aortic strips bathed in Ca-free MOPS-buffered physiological salt solution (PSS). In contrast, forskolin, glyceryl trinitrate and nifedipine each failed to increase tension under identical conditions. Cromakalim also evoked contraction of bovine trachealis muscle bathed in Ca-free PSS. 3 The contractile response to cromakalim, in rabbit aortic strips was of delayed onset (15-20 min) and reached a plateau after approximately 120 min (1.8 g maximum with 1 f1M cromakalim). No cromakalim-induced tension changes were observed in either 1 mM or 2.5 mM Ca-containing PSS. 4 Raising the [KCI] of the Ca-free PSS to 65.9 mM fully inhibited the cromakalim-induced contraction in rabbit aortic strips. In addition, pretreatment of aortic strips with the sulphonylurea glibenclamide antagonized the subsequent mechanical response to cromakalim.5 In Ca-free PSS, cromakalim (1 tiM) stimulated 42K-efflux with a time-course corresponding to the contractile event. Glibenclamide (1 jLM) inhibited this cromakalim-induced 42K-efflux.6 In sharp microelectrode studies in bovine trachealis, cromakalim (10 lM) produced a sustained membrane hyperpolarization in normal PSS. In contrast, the cromakalim-induced hyperpolarization in Ca-free PSS was not sustained. The fading of the hyperpolarization was temporally correlated with the increase in tension under these experimental conditions. 7 It is concluded that the K-channel opener-induced smooth muscle contractile response revealed in Ca-free PSS is the consequence of K-channel opening. The nature of the detailed mechanism which underlies this contractile phenomenon remains to be determined.

show abstract

Effects of several potassium channel openers and glibenclamide on the uterus of the rat

Cited by 56 publications

References 21 publications

Effects of metabolic inhibition and changes of intracellular pH on potassium permeability and contraction of rat uterus.

Effects of metabolic inhibition and changes of intracellular pH on potassium permeability and contraction of rat uterus.

Antagonism of relaxin by glibenclamide in the uterus of the rat in vivo

Characteristics of the contractile response of rabbit aorta produced by cromakalim in calcium‐free solution

Contact Info

Product

Resources

About