Demonstration of some of the physiological properties of rat relaxin

Bradshaw, Jane M. C.; Downing, Sandra J.; Moffatt, Anne; Hinton, Janice C.; Porter, D. G.

doi:10.1530/jrf.0.0630145

Cited by 29 publications

(15 citation statements)

References 14 publications

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“…The results of this study demonstrate that relaxin specifically inhibits contractions in the circular layer of the myometrium by abolishing the plateau component INTRODUCTION It has been shown that exogenous relaxin inhibits uterine contractions in many species (rat: Sawyer, Frieden & Martin, 1953;Bradshaw, Downing, Moffatt, Hinton & Porter, 1981; mouse: Wiqvist, 1959; hamster: Khaligh, 1968; human: Szlachter, O'Byrne, Goldsmith, Steinetz & Weiss, 1980;guinea-pig: Porter, 1972; sheep: Porter, Lye, Bradshaw & Kendall, 1981). Since the first report describing the amino acid sequence ofpurified porcine relaxin (James, Niall, Kwok & Bryant-Greenwood, 1977) and its tertiary structure (Isaacs, James, Niall, Bryant-Greenwood, Dodson, Evans & North, 1978) attention has turned towards gene isolation, synthesis and sequencing of human relaxin by use of an homologous porcine relaxin cDNA probe (Hudson, Haley, John, Cronk, Crawford, Haralambidis, Tregear, Shine & Niall, 1983).…”

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Relaxin inhibits the plateau component of the action potential in the circular myometrium of the rat.

Chamley

Parkington²

1984

The Journal of Physiology

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SUMMARY1. The effects ofrelaxin on contractility and membrane potential ofthe longitudinal and circular smooth muscle layers of the uterus have been studied in vitro using oestrogen-treated, non-pregnant rats and pregnant rats.2. Relaxin decreased the amplitude of contractions induced by electrical stimulation of longitudinal myometrium by decreasing the duration of the bursts of action potentials. This effect was transient and tachyphylaxis always developed and was observed following injection of steroids and up to day 17 of pregnancy. There was no inhibition of tissues from rats from day 18 of pregnancy to term. The peptide had no effect on resting membrane potential, space constant or time constant.3. Action potentials recorded from circular myometrium of non-pregnant rats pre-treated with oestrogen consisted of an initial spike or short burst of spikes followed by a prolonged plateau of depolarization. Spontaneous action potentials and associated contractions were abolished within 2 min of exposure to relaxin (10-8 g/ml) while contractions of much smaller amplitude could be evoked with depolarizing current pulses. This effect was associated with depression of the plateau component of the action potential whereas the spike component was left intact. Relaxin had no effect on passive membrane properties.4. The action potentials of circular myometrium of rats up to day 21 of pregnancy were qualitatively similar to those recorded in the same muscle layer from oestrogentreated, non-pregnant rats and the plateau component was also blocked by relaxin in these tissues. Bursts of spikes were observed in circular strips 24-36 h before parturition, and the effect of the peptide on these was a transient inhibition similar to that observed in longitudinal myometrium.5. Oxytocin increased the amplitude of the spike and the amplitude and duration of the plateau. Relaxin abolished the plateau in the presence of 10-11 and 10-10 Moxytocin but was ineffective when the concentration of the spasmogen was increased further. Prostaglandin F2. increased the amplitude and duration of the plateau.Relaxin abolished the responses to 10-10 and 10-9 M-prostaglandin F2a.6. The results of this study demonstrate that relaxin specifically inhibits contractions in the circular layer of the myometrium by abolishing the plateau component

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confidence: 89%

Relaxin inhibits the plateau component of the action potential in the circular myometrium of the rat.

Chamley

Parkington²

1984

The Journal of Physiology

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“…Relaxin, a polypeptide hormone of molecular weight 6500 daltons, is a potent, selective and reversible inhibitor of uterine contractions in vivo and in vitro (Porter et al, 1979;Sanborn et al, 1980;Cheah & Sherwood, 1981;Bradshaw et al, 1981). Relaxin has been shown to be important for the maintenance of myometrial quiescence during late pregnancy in the rat (Downing & Sherwood, 1985a,b) and for delivery of live young in the rat and pig (Nara et al, 1982;Downing & Sherwood, 1985a).…”

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confidence: 99%

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

Downing

Hollingsworth

1991

British J Pharmacology

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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.

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“…Relaxin, a peptide hormone produced mainly in the ovary, has several target tissues, including the myometrium on which it exerts a relaxant effect (rat : Sawyer et al, 1953;Bradshaw et al, 1981;mouse: Wiqvist, 1959;man: Szlachter et al, 1980;guinea-pig: Porter, 1972; mini-pig: Porter & Watts, 1986). It was recently reported that porcine relaxin specifically depressed the plateau component of the action potential in the myometrium of the pregnant and oestrogen-treated rat, thereby inhibiting the contraction (Chamley & Parkington, 1984).…”

Section: Introductionmentioning

confidence: 99%

Effects of porcine relaxin on contraction, membrane response and cyclic AMP content in rat myometrium in comparison with the effects of isoprenaline and forskolin

Osa

Inoue

Okabe

1991

British J Pharmacology

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1 The longitudinal muscle from the uterus of oestrogen-treated rats was quiescent in Mg-free Krebs solution. Electrical stimulation generated phasic contraction, which was depressed to 35% and 18% by 50 mu and 150 mu porcine relaxin, respectively. 2 The phasic contractions were more strongly depressed to 26% by 50 mu relaxin in solution containing 0.6 mm Mg, and the depression lasted for more than 4 h after the removal of relaxin. During the persisting depression, raising the external Ca to 7.5 mm did not restore the contraction, but the contraction was restored by removal of Mg. 3 The depression of the phasic contraction by relaxin, examined in Mg-free solution, was enhanced and reduced by pretreatment of the tissue with 0.6 mm Mg and 0.6 mm Mn, respectively, for about 15min. In contrast, the depression of contraction by isoprenaline or forskolin was enhanced by pretreatment with either Mg or Mn. 4 The cellular content of cyclic AMP was measured in Krebs solution containing 0.6 mm Mg. The values were 1.24 (pmolmg-' protein) in control solution, and 2.31 and 1.56 when the tissues were treated with 150 mu relaxin and 10-9 M isoprenaline, respectively. 5 The cyclic AMP production in response to 10-7M forskolin measured in Mg-free solution was enhanced when the tissue was pretreated with either 0.6mm Mg or Mn for 15min. The cyclic AMP production in response to 100mu relaxin was increased when the tissue was pretreated with 0.6mm Mg, and was unchanged by pretreatment with Mn. The cyclic AMP production in response to 10-9M isoprenaline was unchanged by pretreatment with the divalent cations. 6 The membrane potential of the muscle was -60.8mV in Krebs solution containing 0.3mm Mg, and electrical stimulation induced an action potential which consisted of spike and plateau components. Application of 150mu relaxin reduced the duration of the plateau; the contractions were progressively depressed. The resting membrane potential and membrane resistance were unchanged by application of 150 mu relaxin. The membrane was hyperpolarized by 2.8 mV, accompanied by a decrease in membrane resistance, when I0-9 M isoprenaline was applied. 7 Although there were several differences between the effects of relaxin and isoprenaline, it is probable that some process, which is cyclic AMP-dependent, accelerated by Mg and depressed by Mn, is involved in the depressant action of relaxin on contraction.

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Demonstration of some of the physiological properties of rat relaxin

Cited by 29 publications

References 14 publications

Relaxin inhibits the plateau component of the action potential in the circular myometrium of the rat.

Relaxin inhibits the plateau component of the action potential in the circular myometrium of the rat.

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

Effects of porcine relaxin on contraction, membrane response and cyclic AMP content in rat myometrium in comparison with the effects of isoprenaline and forskolin

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