Mu opioid receptor expression and localisation in murine spermatozoa and its role in IVF

2020 ◽  
Vol 32 (4) ◽  
pp. 349
Author(s):  
Estibaliz Olabarrieta ◽  
Lide Totorikaguena ◽  
Jon Romero-Aguirregomezcorta ◽  
Naiara Agirregoitia ◽  
Ekaitz Agirregoitia
Keyword(s):  
Opioid Receptor ◽  
Mrna Level ◽  
Harmful Effect ◽  
Mu Opioid Receptor ◽  
Receptor Expression ◽  
Endogenous Opioid ◽  
Opioid Agonist ◽  
Mu Opioid ◽  
Fertilisation Rate ◽  
Mature Spermatozoa

The endogenous opioid peptides are reported to be involved in the regulation of reproductive physiology. Many of the studies conclude with statements on the harmful effect of opioids on male fertility but, in fact, there are no studies regarding the real fertilisation potential of spermatozoa that have been exposed to opioids. The aim of the present study was to examine if modulation of mu opioid receptor (OPRM1) in murine spermatozoa during capacitation influenced embryo production after IVF. The presence of OPRM1 in murine mature spermatozoa was analysed by reverse transcription–polymerase chain reaction and immunofluorescence. We analysed the involvement of OPRM1 on IVF and pre-implantational embryo development by incubating the spermatozoa with the opioid agonist morphine and/or antagonist naloxone. We verified the presence of OPRM1 in murine mature spermatozoa, not only at the mRNA level but also the protein level. Moreover, incubation of the spermatozoa with morphine, before IVF, had an effect on the fertilisation rate of the spermatozoa and reduced the numbers of blastocysts, which was reversed by naloxone. Considering that opioids are widely used clinically, it is important to take into account their effect, via OPRM1, on the fertility of patients.

scholarly journals Regulation of Mu Opioid Receptor Expression in Developing T Cells

2012 ◽  
Vol 7 (4) ◽  
pp. 835-842 ◽  
Author(s):  
Lily Zhang ◽  
Judith Sliker Belkowski ◽  
Tammi Briscoe ◽  
Thomas J. Rogers
Keyword(s):  
T Cells ◽  
Opioid Receptor ◽  
Mu Opioid Receptor ◽  
Receptor Expression ◽  
Mu Opioid

Lithium alters mu-opioid receptor expression in the rat brain

2000 ◽  
Vol 279 (1) ◽  
pp. 9-12 ◽  
Author(s):  
J.M de Gandarias ◽  
I Acebes ◽  
E Echevarrı́a ◽  
L Vegas ◽  
L.C Abecia ◽  
...  
Keyword(s):  
Rat Brain ◽  
Opioid Receptor ◽  
Mu Opioid Receptor ◽  
Receptor Expression ◽  
Mu Opioid

scholarly journals Single-nucleotide polymorphism in the human mu opioid receptor gene alters β-endorphin binding and activity: Possible implications for opiate addiction

1998 ◽  
Vol 95 (16) ◽  
pp. 9608-9613 ◽  
Author(s):  
Cherie Bond ◽  
K. Steven LaForge ◽  
Mingting Tian ◽  
Dorothy Melia ◽  
Shengwen Zhang ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Methadone Maintenance ◽  
Receptor Gene ◽  
Mu Opioid Receptor ◽  
Coding Region ◽  
Allelic Form ◽  
Endogenous Opioid ◽  
Single Nucleotide ◽  
Allele Distribution ◽  
Mu Opioid

Opioid drugs play important roles in the clinical management of pain, as well as in the development and treatment of drug abuse. The mu opioid receptor is the primary site of action for the most commonly used opioids, including morphine, heroin, fentanyl, and methadone. By sequencing DNA from 113 former heroin addicts in methadone maintenance and 39 individuals with no history of drug or alcohol abuse or dependence, we have identified five different single-nucleotide polymorphisms (SNPs) in the coding region of the mu opioid receptor gene. The most prevalent SNP is a nucleotide substitution at position 118 (A118G), predicting an amino acid change at a putative N-glycosylation site. This SNP displays an allelic frequency of approximately 10% in our study population. Significant differences in allele distribution were observed among ethnic groups studied. The variant receptor resulting from the A118G SNP did not show altered binding affinities for most opioid peptides and alkaloids tested. However, the A118G variant receptor binds β-endorphin, an endogenous opioid that activates the mu opioid receptor, approximately three times more tightly than the most common allelic form of the receptor. Furthermore, β-endorphin is approximately three times more potent at the A118G variant receptor than at the most common allelic form in agonist-induced activation of G protein-coupled potassium channels. These results show that SNPs in the mu opioid receptor gene can alter binding and signal transduction in the resulting receptor and may have implications for normal physiology, therapeutics, and vulnerability to develop or protection from diverse diseases including the addictive diseases.

Optimisation of human mu opioid receptor expression in baculovirus-infected insect cells

1999 ◽  
Vol 27 (5) ◽  
pp. A151-A151
Author(s):  
Massotte Dominique ◽  
Baroche Laurence ◽  
Pereira Carlos ◽  
Suply Thomas ◽  
Perret Bénédicte ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Insect Cells ◽  
Mu Opioid Receptor ◽  
Receptor Expression ◽  
Mu Opioid ◽  
Infected Insect

scholarly journals Evaluation of Mu Opioid Receptor Expression via Immunohistochemistry in Various Tumor Types

2015 ◽  
Vol 2 (2) ◽  
Author(s):  
Jolanta Jedrzkiewicz ◽  
Tyler R. Call ◽  
Sheryl R. Tripp ◽  
Benjamin L. Witt
Keyword(s):  
Opioid Receptor ◽  
Mu Opioid Receptor ◽  
Receptor Expression ◽  
Mu Opioid ◽  
Tumor Types

Dilemma of Addiction and Respiratory Depression in the Treatment of Pain: A Prototypical Endomorphin as a New Approach

Pain Medicine ◽  
2019 ◽  
Vol 21 (5) ◽  
pp. 992-1004 ◽  
Author(s):  
Lynn Webster ◽  
William K Schmidt
Keyword(s):  
Side Effects ◽  
Respiratory Depression ◽  
Opioid Receptor ◽  
Severe Pain ◽  
Mu Opioid Receptor ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid ◽  
Mu Opioid ◽  
Receptor Agonists ◽  
Opioid Receptor Agonists

Abstract Objective Although mu-opioid receptor agonists have been the mainstay of analgesic regimens for moderate to severe pain, they are associated with serious side effects, risks, and limitations. We evaluate the most serious risks associated with conventional opioids and compare these with the pharmacology of CYT-1010, a prototypical endomorphin and mu-opioid receptor agonist. Results Addiction and respiratory depression are serious risks of traditional mu-opioid analgesics. Mitigation strategies have been inadequate at addressing the opioid crisis and may interfere with the effective treatment of pain. Improved understanding of mu-opioid receptor biology and the discovery in 1997 of an additional and unique family of endogenous opioid peptides (endomorphins) have provided a pathway for dissociating analgesia from opioid-related adverse events and developing new classes of mu-opioid receptor agonists that use biased signaling and/or target novel sites to produce analgesia with reduced side effect liability. Endomorphin-1 and -2 are endogenous opioid peptides highly selective for mu-opioid receptors that exhibit potent analgesia with reduced side effects. CYT-1010 is a cyclized, D-lysine-containing analog of endomorphin-1 with a novel mechanism of action targeting traditional mu- and exon 11/truncated mu-opioid receptor 6TM variants. CYT-1010 preclinical data have demonstrated reduced abuse potential and analgesic potency exceeding that of morphine. In an initial phase 1 clinical study, CYT-1010 demonstrated significant analgesia vs baseline and no respiratory depression at the dose levels tested. Conclusions CYT-1010 and other novel mu-opioid receptor agonists in clinical development are promising alternatives to conventional opioids that may offer the possibility of safer treatment of moderate to severe pain.

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