Antagonistic property of buprenorphine for putative ϵ-opioid receptor-mediated G-protein activation by β-endorphin in pons/medulla of the μ-opioid receptor knockout mouse

  title={Antagonistic property of buprenorphine for putative ϵ-opioid receptor-mediated G-protein activation by $\beta$-endorphin in pons/medulla of the $\mu$-opioid receptor knockout mouse},
  author={Hirokazu Mizoguchi and H.-e. Wu and Minoru Narita and F. Scott Hall and Ichiro Sora and George R. Uhl and Hiroshi Nagase and Leon F. Tseng},
Abstract β-Endorphin is a non-selective opioid peptide which binds μ-, δ- and putative ϵ (β-endorphin-sensitive non-μ-, non-δ- and non-κ 1 -)-opioid receptors. We have previously reported that β-endorphin-produced G-protein activation is mediated by the stimulation of both μ- and putative ϵ-opioid receptors. The present study was designed to further characterize this putative ϵ-opioid receptor-mediated G-protein activation in the pons/medulla membrane obtained from mice lacking μ-opioid… Expand
Buprenorphine Blocks ϵ- and μ-Opioid Receptor-Mediated Antinociception in the Mouse
It is concluded that buprenorphine, at small doses, blocks ϵ-opioid receptor-mediated β-endorphin-induced antinociception and μ-opionceptor-mediated DAMGO-inducedAntagonistic properties, and at high doses produces a μ-OPioid receptors-mediated antinOCiception. Expand
Loss of μ-opioid receptor-mediated G-protein activation in the pons/medulla of mice lacking the exons 2 and 3 of μ-opioid receptor gene
The present results suggest that MOR that is created from the sequences encoded with exons 2 and 3 of the MOR gene, as has been previously observed in studies of mice lacking exon 1 of this gene, may be another critical target for the activation of G-protein by MOR agonists in the mouse pons/medulla. Expand
Differential mechanism of G-protein activation induced by endogenous mu-opioid peptides, endomorphin and beta-endorphin.
The subject of the present review is to focus on the differential mechanism underlying G-protein activation induced by these mu-opioid peptides using the [35S]GTPgammaS binding assay. Expand
Non-opioid actions of opioid peptides.
This work has investigated Met-enkephalin-Arg-Phe (MERF) and its analogues by the means of direct and indirect radioligand binding assays and found that in addition to kappa(2) and delta-opioid receptors, MERF can act also through sigma(2)- or probably via FMRF-NH( 2) receptors in rat cerebellum. Expand
In vivo and in vitro characterization of naltrindole-derived ligands at the κ-opioid receptor
Interestingly, while 5’-AMN and 5'-MABN were not κ-selective, both compounds did show significant antidepressant- and anxiolytic-like effects at 7–14 days post-injection in mice, contrary to the hypothesis. Expand
No evidence for G-protein-coupled epsilon receptor in the brain of triple opioid receptor knockout mouse.
It is concluded that the brain epsilon site involves mu, delta and/or kappa receptors, possibly coupled to nonclassical G proteins. Expand
Effects of beta-endorphin on endothelial/monocytic endothelin-1 and nitric oxide release mediated by mu1-opioid receptors: a potential link between stress and endothelial dysfunction?
A role of beta-Endorphin is hypothesized in the pathogenesis of stress-induced endothelial dysfunction through peripherally circulating beta-endorphin, which may offset the balance of vasoactive mediators, leading to an unopposed vasoconstriction. Expand
Recent Advances in the Search for the -Opioidergic System
The newly discovered endogenous μ-opioid receptor (MOP-R) ligands endomorphin-1 (EM-1) and -2 (EM-2) exhibit the highest specificity and affinity for the MOP-R of any endogenous substance so farExpand
Differential effects of gestational buprenorphine, naloxone, and methadone on mesolimbic mu opioid and ORL1 receptor G protein coupling.
These findings on mu opioid receptor (MOR) GTP-binding regulatory protein (G protein) coupling and its gender dependency are consistent with earlier studies on mu receptor binding adaptation induced by buprenorphine in dams and neonatal rats after in utero treatment regimens, and they extend the gestational effects of this opiate to mu and N/OFQ receptor functionality. Expand
Selective impairment of spinal mu-opioid receptor mechanism by plasticity of serotonergic facilitation mediated by 5-HT2A and 5-HT2B receptors
Results indicate that plasticity of spinal serotonergic neurotransmission can selectively reduce spinal MOR mechanisms via 5‐HT2A and 5‐ HT2B receptors, including upregulation of the latter and increased expression in dorsal horn neurons containing MOR. Expand


Activation of G-proteins in the mouse pons/medulla by β-endorphin is mediated by the stimulation of μ- and putative ε-receptors
Abstract The activation of μ-, δ- and κ 1 -opioid receptors by their respective agonists increases the binding of the non-hydrolyzable GTP analog guanosine-5′-(γ-thio)-triphosphate (GTPγS) to GExpand
The μ-opioid receptor gene-dose dependent reductions in G-protein activation in the pons/medulla and antinociception induced by endomorphins in μ-opioid receptor knockout mice
Abstract There appear to be different relationships between μ-opioid receptor densities and the acute and neuroadaptive μ-opioid agonist-induced responses of the multiple opioid neuronal systems,Expand
β-Endorphin-(1–27) antagonizes β-endorphin- but not morphine-, D-PEN2-D-PEN2-enkephalin- and U50, 488H-induced analgesia in mice
β-Endorphin-(1–27), administered intraventricularly has been previously reported to block the analgesia induced by β-endorphin injected intraventricularly. The present study was to determine if theExpand
mu-Opioid receptor-stimulated guanosine-5'-O-(gamma-thio)-triphosphate binding in rat thalamus and cultured cell lines: signal transduction mechanisms underlying agonist efficacy.
The results suggest that mu-opioid agonist efficacy is determined by the magnitude of the receptor-mediated affinity shift in the binding of GTP (or[35S]GTP gamma S) versus GDP to the G protein and by the number of G proteins activated per occupied receptor. Expand
Differential antinociceptive effects of endomorphin-1 and endomorphin-2 in the mouse.
It is proposed that endomorphin-1 produces antinociception by stimulating one type of mu-opioid receptor, whereas endomorphicin-2 initially stimulates different mu-OPioid receptors, which subsequently induce the release of dynorphins that act on kappa-opIOid receptors to produce antinOCiception. Expand
A potent and selective endogenous agonist for the µ-opiate receptor
Peptides have been identified in mammalian brain that are considered to be endogenous agonists for the δ (enkephalins) and κ (dynorphins) opiate receptors, but none has been found to have anyExpand
Delta opioid modulation of the binding of guanosine-5'-O-(3-[35S]thio)triphosphate to NG108-15 cell membranes: characterization of agonist and inverse agonist effects.
The ability of the delta opioid agonist DPDPE to stimulate binding of the GTP analog guanosine-5'-O-(3-[35S]thio)triphosphate to pertussis toxin-sensitive G proteins has been characterized in membranes from NG108-15 mouse neuroblastoma X rat glioma cells. Expand
Antagonist-induced up-regulation of the putative epsilon opioid receptor in rat brain: comparison with kappa, mu and delta opioid receptors.
It is reported that chronic treatment with the opiate antagonist naltrexone dramatically increases the number of non-mu, non-delta,non-kappa binding sites in rat brain, as well as theNumber of mu, delta and kappa receptors. Expand
Modulation by mu-opioid agonists of guanosine-5'-O-(3-[35S]thio)triphosphate binding to membranes from human neuroblastoma SH-SY5Y cells.
The ability of mu-opioid agonists to activate G proteins has been demonstrated by studying the binding of the GTP analogue guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTP gamma S) to membranesExpand
Spinal analgesic actions of the new endogenous opioid peptides endomorphin‐1 and ‐2
It is concluded that the endomorphins are potent spinal antinociceptive and anti-allodynic agents and that they or related compounds may prove therapeutically useful as spinal analgesics. Expand