Now showing 1 - 3 of 3
  • Publication
    A role for adrenergic receptors in the uterotonic effects of ergometrine in isolated human term non-laboring myometrium
    Background: Ergometrine is a uterotonic agent that is recommended in the prevention and management of post partum hemorrhage. Despite its long-standing use the mechanism by which it acts in humans has never been fully elucidated. The objective of this study was to investigate the role of adrenoreceptors in ergometrine's mechanism of action in human myometrium. The study examined the hypothesis that alpha adrenoreceptor antagonism would result in the reversal of the uterotonic effects of ergometrine. Methods: Myometrial samples were obtained from women undergoing elective cesarean delivery. The samples were then dissected into strips and mounted in organ bath chambers. Following generation of an ergometrine concentration-response curve (10-15 to 10-5 M), strips were treated with increasing concentrations of ergometrine (10-15 to 10-7 M) alone and ergometrine (10-7 to 10-5 M) in the presence of phentolamine (10-7 M), prazosin (10-7 M), propranolol (10-6 M) or yohimbine (10-6 M). The effects of adding ergometrine and the effect of drug combinations were analysed using linear mixed effects models with measures of amplitude (g), frequency (contractions/10min) and motility index (g*contractions/10min). Results: A total of 157 experiments were completed on samples obtained from 33 women. There was a significant increase in the motility index (adding 0.342 g*counts/10min/µM; 95% CI from 0.253 to 0.431, P<0.001), amplitude (0.078 g/µM; 95% CI, from 0.0344 to 0.121, P=5e-04) and frequency (0.051 counts/10min/µM; 95% CI, 0.038 to 0.063, P<0.001) in the presence of ergometrine. The α adrenergic antagonist phentolamine and the more selective α1 adrenergic antagonist prazosin, inhibited the ergometrine mediated increase in motility index, amplitude and frequency (-1.63 g*counts/10mins/µM and -16.70 g*counts/10mins/µM for motility index, respectively). Conclusions: These results provide novel evidence for a role for α adrenergic signaling mechanisms in the action of ergometrine on human myometrial smooth muscle in the in vitro setting. Information that sheds light on the mechanism of action of ergometrine may have implications for the development of further uterotonic agents.
      538Scopus© Citations 8
  • Publication
    A comparison of the effects of lindane and FeCl3/ADP on spontaneous contractions in isolated rat and human term myometrium
    Oxidative stress affects the contractile behavior of smooth muscle resulting in complications during labor. Toxicants such as lindane and ferric chloride (FeCl3)/adenosine diphosphate (ADP) cause oxidative stress and have previously been shown to inhibit smooth muscle contraction. In this study we examined the effects of the oxygen species scavengers, ascorbic acid and N-acetylcysteine on lindane and FeCl3/ADP’s inhibition of spontaneous myometrial contractions in rat and human myometrium. Lindane and FeCl3/ADP gave rise to concentration-dependent reductions in rat (EC50 11.8 × 10−6 M and 0.9 × 10−3 M) and human myometrial contractions (EC50 16.3 × 10−6 M and 1.1 × 10−3 M, respectively). Pre-treatment with N-acetylcysteine significantly increased the EC50 for the effects of lindane on motility index of human tissue and reduced the maximum inhibitory effect of FeCl3/ADP on contractions in both rat and human myometrium. Ascorbic acid reduced the effects of FeCl3/ADP in rat tissue only. In conclusion pre-treatment with specific antioxidants may protect both rat and human myometrium from the inhibitory effects of lindane and FeCl3/ADP.
      148Scopus© Citations 1
  • Publication
    Opioid mediated activity and expression of mu and delta opioid receptors in isolated human term non-laboring myometrium
    The existence of opioid receptors in mammalian myometrial tissue is now widely accepted. Previously enkephalin degrading enzymes have been shown to be elevated in pregnant rat uterus and a met-enkephalin analogue has been shown to alter spontaneous contractility of rat myometrium. Here we have undertaken studies to determine the effects of met-enkephalin on in vitro human myometrial contractility and investigate the expression of opioid receptors in pregnant myometrium. Myometrial biopsies were taken from women undergoing elective caesarean delivery at term. Organ bath experiments were used to investigate the effect of the met-enkephalin analogue [d-Ala 2, d-met 5] enkephalin (DAMEA) on spontaneous contractility. A confocal immunofluorescent technique and real time PCR were used to determine the expression of protein and mRNA, respectively for two opioid receptor subtypes, mu and delta. DAMEA had a concentration dependent inhibitory effect on contractile activity (1×10−7 M–1×10−4 M; 54% reduction in contractile activity, P<0.001 at 1×10−4 M concentration). Mu and delta opioid receptor protein sub-types and their respective mRNA were identified in all tissues sampled. This is the first report of opioid receptor expression and of an opioid mediated uterorelaxant action in term human non-labouring myometrium in vitro
      938Scopus© Citations 6