Opioid peptides inhibit the action of oestradiol on human myometrial cells in culture

Abstract

The effect of opioid peptides on cultured, oestradiol-stimulated human myometrial cells was examined. Oestradiol increased cell densities in mixed-cell (smooth muscle cells + stromal fibroblasts) cultures by 40%. This oestradiol-induced stimulation of cell proliferation was decreased to control values by D-met2-pro5-enkephalinamide. The half-effective inhibitory concentration of enkephalinamide was 0.3 nmol/l. The opioid-induced inhibition of cell proliferation was blocked completely by the specific opiate receptor antagonist naloxone, while naloxone did not have any effect on its own. This opioid effect was mediated dominantly by the mu opiate receptor. The optimal concentration for oestradiol to stimulate uterine cell proliferation was 2.2 nM. The basal rate of cell proliferation was not affected by enkephalinamide. In saturation experiments, the parameters of specific [3H]-naloxone binding were: dissociation constant = 1.02 nM, maximal binding capacity = 2910 binding sites/cell, Hill coefficient = 1.029. In human myometrial pure smooth muscle cell cultures, oestradiol decreased the proliferation of cells. Progesterone potentiated these oestradiol effects, but had no effect on its own. Enkephalinamide was also able to block the effects of oestradiol, but naloxone did not antagonize it. In summary, here we present a novel inhibitory role of endogenous opioid peptides in the regulation of cell growth and proliferation in the human uterus.

Developmental changes in the inhibition of cultured rat uterine cell proliferation by opioid peptides

“…Similar to previous results (Környei et al . 1997, 1999, 2001), the stimulated cell proliferation in 60‐day‐old adult animals was inhibited by ENK and DAMGO, suggesting that the mu opioid receptor is involved in the anti‐proliferative effect of opioid peptides.…”

“…Similar to previous observations on uterine cells from adults (Környei et al . 1997, 1999, 2001), the half‐inhibitory concentration of ENK was found to be 0.3 n m , i.e.…”

“…2000; Környei et al . 2001) mitogenic actions in rat uterine and in human myometrial cells (Környei et al . 1999).…”

“…2000; Zagon et al . 2002), and with the mu (Környei et al . 1997, 1999, 2001) and kappa (Chatzaki et al .…”

99mTc Bağlı Yeni Bir Peptid: Ratlarda 99m Tc β-Kazomorphin 6 Molekülünün Biyodistrübisyon ve Görüntüleme Çalışması

“…β-casomorphin release from parent protein molecule during gastrointestinal digestion. It was reported that uterus and ovary express opioid receptors [17,18] . Animal studies show that β-casomorphins can act as opioid receptor agonists are derived-casein.…”