Nuclear expression of μ‐opioid receptors in a human mesothelial cell line

Abstract

1 Possibly acting via mu-opioid receptors (MORs), morphine inhibits the formation of experimentally induced postoperative abdominal adhesions in rats. Mesothelial cells may participate in adhesion formation by secreting mediators that interfere negatively with fibrinolysis. Morphine may prevent adhesions by inhibiting the release of pro-adhesion mediators from mesothelial cells. This study aimed to investigate whether human mesothelial cells express MOR-1; if so, such could constitute a site of action for morphine in adhesion prevention. 2 Cells from Met-5A, a human mesothelial cell line were seeded and prepared for immunocytochemistry and Western blotting. 3 Immunocytochemistry showed MOR-1 expression in mesothelial cells, predominantly in the nuclei. Western blotting showed two bands (c. 35 and 50 kDa) which correspond to those obtained with a control lysate from cells known to express MORs. In addition, we found MOR-1 expression with nuclear and cytoplasmatic localization in biopsies from human abdominal adhesions. 4 The current findings may suggest that morphine could interact directly with mesothelial cells via MOR-1 receptors, and thereby modulate adhesion formation, possibly by interfering with the release of pro-adhesion factors from these cells.

Opioid-receptor gene expression and localization in cancer cells

“…For instance, the presence of MOR in cell nuclei was reported by Nylund et al [18] in colon HT-29 cells and by KhorramManesh et al [19] in human mesothelial Mer-5A cells. In contrast to these results, we did not identify opioid receptors in the nucleus of HT-29 cells.…”

Changes in the expression of the μ-opioid receptor in the mare oviduct during oestrus and anoestrus

“…Immunostaining of the nucleus of ciliated cells is was expected since immunohistochemical localization of nuclear MOR has been found in NG108-15 neurohybrid cells (Belcheva et al, 1993), human colon tissue and colon cancer cell lines (Nylund et al, 2008), and human mesothelial cell lines (Khorram-Manesh et al, 2009). The detection of nuclear MOR that belongs to the class of G-proteincoupled receptors (Sanders et al, 2008), was justified with the presence on nuclear membranes of G-proteincoupled binding sites (Boivin et al, 2008).…”

“…Although MOR has been immuno-localized mainly in the nervous system, the expression of this opioid receptor has been shown by means of immunohistochemical studies in other tissues, such as pancreas and liver (Khawaja et al, 1990), gastrointestinal tract (Lang et al, 1996;Bagnol et al, 1997;Fickel et al, 1997), follicular cells and pre-implantation mouse embryos (Kalyuzhny et al, 1997), keratinocytes (Bigliardi et al, 1998;Bigliardi-Qi et al, 1999, 2004, kidney (Di Sole et al, 2001), cumulusoocyte complex (Dell'Aquila et al, 2002, inner ear (Popper et al, 2004), pituitary (Carretero et al, 2004), pineal gland (Phansuwan-Pujito et al, 2006 and sperm cells (Agirregoitia et al, 2006;Albrizio et al, 2006), human colon tissue (Nylund et al, 2008) and mesothelial cell lines (Khorram-Manesh et al, 2009). As regards the horse, MOR has been immuno-localized in synovial membranes (Sheehy et al, 2001), ejaculated spermatozoa (Albrizio et al, 2005), cumulus-oocyte complex (Dell'Aquila et al, 2008) and oviductal isthmus (Desantis et al, 2008).…”

Location Bias as Emerging Paradigm in GPCR Biology and Drug Discovery

“…Endogenous nucleus-localized GPCRs such as a 1A & B -AR (Wright et al, 2008), MT2 (Lanoix et al, 2006) and MOR 1 (Khorram-Manesh et al, 2009) are directly targeted to this compartment without appearing at the PM. These GPCRs could originate via two main sources.…”