Mutational analysis of the structure and function of opioid receptors

Law, Ping Yee; Wong, Yung Hou; Loh, Horace H.

doi:10.1002/(sici)1097-0282(1999)51:6<440::aid-bip6>3.0.co;2-t

Cited by 66 publications

(47 citation statements)

References 119 publications

(137 reference statements)

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“…The following characteristics of the deduced amino acid sequence supported the GPCR classification: the presence of seven hydrophobic regions that share sequence identity with the membrane-spanning domains of GPCRs (Minami & Satoh 1995, Law et al 1999; asparagine residues within the N-terminal domain that function as potential sites for N-linked glycosylation (Minami & Satoh 1995); cysteine residues in the intracellular C-terminal domain that are potential palmitoylation sites (Ovchinnikov et al 1988, O'Dowd et al 1989; and two cysteine residues, located in extracellular loops 1 and 2, that may connect the loops by forming a disulfide bridge (Dixon et al 1987, Karnik et al 1988). In addition, there are a number of serine and threonine residues in the putative cytoplasmic regions, presenting potential sites for phosphorylation by protein kinases.…”

Section: Discussionmentioning

confidence: 96%

Cloning, pharmacological characterization and tissue distribution of an ORL1 opioid receptor from an amphibian, the rough-skinned newt Taricha granulosa

Walthers¹,

Bradford²,

Moore³

2005

Journal of Molecular Endocrinology

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We have cloned and characterized an opioid receptor-like (ORL1; also referred to as NOP) receptor from a urodele amphibian, the rough-skinned newt Taricha granulosa The cDNA clone encodes a protein of 368 amino acids that contains the seven hydrophobic domains characteristic of G-protein-coupled receptors, and has the highest sequence identity to the frog (Rana pipiens) nociceptin-like and human ORL1 opioid receptors (79·6 and 68·4%, respectively). Saturation binding assays on membranes from COS-7 cells transiently expressing the newt ORL1 (nORL) receptor revealed a single, high-affinity (estimated K d , 0·1974 nM) binding site for the ORL1-specific agonistIn competition binding assays, the [ 3 H]oFQ-binding site, like the mammalian ORL1 receptor, had no affinity for the non-selective opioid receptor antagonist naloxone, the -selective agonists U69593 and U50488, or the µ-and -selective opioid receptor agonists DAMGO and DPDPE, respectively. However, the nORL receptor displayed higher affinities for the -selective agonists dynorphin A (1-13), dynorphin B, and dynorphin A (1-8) (K i values, 2·8, 151·8, and 183·0 nM, respectively) than its mammalian homologue. The tissue distribution of the nORL receptor, as determined by reverse transcriptase PCR, was also found to differ from reports on the mammalian ORL1 receptor, with mRNA detected in brain, spinal cord, and lung, but not detected in a number of other peripheral tissues reported to express the receptor in mammals. This is the first report describing the expression and characterization of an amphibian ORL1 receptor, and contributes to our understanding of the evolution of the opioid system.

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Section: Discussionmentioning

confidence: 96%

Cloning, pharmacological characterization and tissue distribution of an ORL1 opioid receptor from an amphibian, the rough-skinned newt Taricha granulosa

Walthers¹,

Bradford²,

Moore³

2005

Journal of Molecular Endocrinology

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“…Agonist-induced receptor phosphorylation of the carboxyl tail is frequently involved in receptor desensitization. Several laboratories reported (see review by Law et al (Law et al, 1999) that mutations and/or deletions of residues or motifs in the carboxyl terminal tail of MOP resulted in changes of function, regulation and trafficking of the receptor. For example, mutation of Ser356 and Ser363 to alanine attenuated agonist-induced MOP downregulation without having any effect on receptor phosphorylation (Burd et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Chronic morphine treatment up-regulates mu opioid receptor binding in cells lacking filamin A

Onoprishvili

Simon

2007

Brain Research

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We investigated the effects of morphine and other agonists on the human mu opioid receptor (MOP) expressed in M2 melanoma cells, lacking the actin cytoskeleton protein filamin A and in A7, a sub clone of the M2 melanoma cells, stably transfected with filamin A cDNA. The results of binding experiments showed, that after chronic morphine treatment (24 hr) of A7 cells, MOP binding sites were down-regulated to 63% of control, whereas, unexpectedly, in M2 cells, MOP binding was upregulated to 188% of control naïve cells. Similar up-regulation was observed with the agonists methadone and levorphanol. The presence of antagonists (naloxone or CTAP) during chronic morphine treatment inhibited MOP down-regulation in A7 cells. In contrast, morphine-induced upregulation of MOP in M2 cells was further increased by these antagonists. Chronic morphine desensitized MOP in A7 cells, i.e. it decreased DAMGO-induced stimulation of GTPγS binding. In M2 cells DAMGO stimulation of GTPγS binding was significantly greater than in A7 cells and was not desensitized by chronic morphine. Pertussis toxin treatment abolished morphine-induced receptor up-regulation in M2 cells, whereas it had no effect on morphine-induced down-regulation in A7 cells. These results indicate that, in the absence of filamin A, chronic treatment with morphine, methadone or levorphanol leads to up-regulation of MOP, to our knowledge, the first instance of opioid receptor up-regulation by agonists in cell culture.

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“…Three opioid receptor types, , ␦, and , are known, and they belong to the super family of G-protein-coupled receptors (Minami and Satoh, 1995;Law et al, 1999;Pasternak, 2004). Regulation of their expression has been extensively examined, primarily at the level of gene transcription regulated by vitamin A, cytokines (Bi et al, 2001;Park et al, 2002;Wei and Loh, 2002;Hu et al, 2004), and specific transcription factors (Kraus et al, 2001;Kim et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Netrin-1 Signaling RegulatesDe NovoProtein Synthesis of κ Opioid Receptor by Facilitating Polysomal Partition of Its mRNA

Tsai¹,

Bi²,

Loh³

et al. 2006

J. Neurosci.

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The expression of opioid receptor (KOR) is subjected to both transcriptional and posttranscriptional controls. We report that KOR translation is regulated by netrin-1 in primary neurons of dorsal root ganglion (DRG) and in P19 embryonal carcinoma cells. Without stimulation, a significant portion of KOR mRNA is maintained in a dormant state and partitions in the translationally inactive, postpolysomal fraction. During netrin-1 stimulation, which activates its downstream target focal adhesion kinase (FAK), KOR mRNA rapidly partitions to the translationally active polysomal fraction. Functionally, the newly synthesized KOR proteins in DRG neurons are able to bind to specific ligands. This report describes the first example of netrin-1 signaling in the translational control of a drug receptor KOR, which involves the mediator of netrin-1, FAK, and a novel mechanism that enhances the association of target mRNA with polysomes for translational activation.

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Mutational analysis of the structure and function of opioid receptors

Cited by 66 publications

References 119 publications

Cloning, pharmacological characterization and tissue distribution of an ORL1 opioid receptor from an amphibian, the rough-skinned newt Taricha granulosa

Cloning, pharmacological characterization and tissue distribution of an ORL1 opioid receptor from an amphibian, the rough-skinned newt Taricha granulosa

Chronic morphine treatment up-regulates mu opioid receptor binding in cells lacking filamin A

Netrin-1 Signaling RegulatesDe NovoProtein Synthesis of κ Opioid Receptor by Facilitating Polysomal Partition of Its mRNA

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