Opioid mediated activity and expression of mu and delta opioid receptors in isolated human term non-labouring myometrium

Abstract

TitleOpioid mediated activity and expression of mu and delta opioid receptors in isolated human term non-laboring myometrium AbstractThe 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 (1X10 -7 M to 1X10 -4 M; 54% reduction in contractile activity, P<0.001 at 1X10 -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-laboring myometrium in vitro.

The expression of mRNAs for opioid receptors in endometrium of cyclic and early pregnant pigs; <i>in vitro</i> effects of IL-1β, IL-6 and TNFα

“…Zhu and Pintar (1998) have found μ and κ opioid receptors in the endometrium and myometrium of pregnant mice. Furthermore, μ and δ opioid receptors were identified in woman myometrium (Fanning et al, 2013). The present study demonstrated in vitro the time-depended changes in the basal expression of genes for opioid receptors in the porcine endometrial explants.…”

“…In previous studies, it has been demonstrated that EOPs may be implicated in the regulation of several processes in the uterus such as: its contractility, secretory activity, local immunomodulation, cell proliferation and apoptosis (Petit et al, 1993;Cemerikic et al, 1994;Adjroud, 1995;Környei et al, 1997;Zoumakis et al, 1997;Chatzaki et al, 2001;Fanning et al, 2013). Variable data concerning the modulation of uterine muscle contractility by opioids have been reported for different species and reproductive stages.…”

“…For example, Met-enkephaline analogue (DAMEA) and enkaphalinase inhibitors stimulated the duration and amplitude of spontaneous uterine contractions in rats during late pregnancy and these excitatory effects were blocked by naloxone (Adjroud, 1995). Conversely, DAMEA caused the utero-relaxant effect in terms of human non-labouring myometrium in vitro, reversible by naloxone, which coincided with the presence of μ and δ opioid receptors in the tissue (Fanning et al, 2013). In turn, there was no significant effect of β-endorphin or naloxone on uterine motility in cows during oestrus and dioestrus (Ko et al, 1989).…”

“…The uterine expression of opioid precursor genes and/or opioid peptides in different species, including the pig, has been demonstrated in numerous studies (Dziekoński et al, 2015), but data concerning the presence and regulation of opioid receptors in the uterus are limited (Baraldi et al, 1985;Zhu and Pintar, 1998;Fanning et al, 2013). The present study demonstrated in vitro changes in the expression of mRNAs for opioid receptors in the porcine endometrial explants under the basal conditions as well as in the presence of proinflammatory cytokines (IL-1β, IL-6 and TNFα) during the oestrous cycle and early pregnancy.…”

“…In pregnant mouse, the expression of mRNAs for opioid receptors was demonstrated in the uteroplacental structures by in situ hybridization; μ receptor was identified in the nondecidualized endometrium stromal cells and in the luminal epithelium, κ receptor in the decidual basalis, both μ and κ receptors in myometrium, and δ receptor in the trophoblast giant cells (Zhu and Pintar, 1998). Moreover, the expression of mRNAs and proteins for μ and δ opioid receptors was found in the myometrium of pregnant women (Fanning et al, 2013). However, the expression of opioid receptors has not been studied in the uterus of large domestic animals yet.…”