The Phylogeny of Enkephalins: Speculations on the Origins of Opioid Precursors

Dores, Robert M.; McDonald, Lorraine K.; Goldsmith, Alex; Deviche, Pierre; Rubin, David A.

doi:10.1159/000154686

Cited by 25 publications

(11 citation statements)

References 14 publications

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“…It has been hypothesized that the four opioid precursor genes (proenkephalin, proopiomelanocortin, prodynorphin, and proorphanin) arose by sequential duplication of a common ancestral gene over the past 500 million years, and that the emergence of the cognate receptor proteins ( , µ, , ORL1) paralleled the divergence of the peptide genes (Douglass et al 1984, Dores et al 1993, Danielson & Dores 1999. Recently, the first complete non-mammalian vertebrate proorphanin cDNA gene sequence was obtained from the sturgeon, Acipencer transmontanus (Danielson et al 2001).…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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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“…In jawless fish (lamprey and hagfish), some bony fish (bowfin, gar, lungfish), and in reptiles and birds, the molar ratio of metenkephalin to leu-enkephalin ranged from 2:1 to 9:1 (for review, see Lindberg & White, 1986;Dores et al, 1993). If the analysis had been limited to only these taxa, then the conclusion would have been that the organization of the proenkephalin gene in fish, reptiles, and birds is similar but not identical to that of mammalian proenkephalin.…”

Section: Proenkephalinmentioning

confidence: 99%

“…4; Y 231 -S 235 ). These substitutions would explain why leu-enkephalin has not been detected in extracts of the sturgeon CNS (Dores et al, 1993). Finally, the African lungfish proenkephalin sequence presented in Figure 4 provides another example of a taxon in which leu-enkephalin has been replaced by a met-enkephalin sequence.…”

Section: Proenkephalinmentioning

confidence: 99%

“…Initially, the possibility of dynorphin-related products being present in either ray-finned or lobe-finned fish had been dismissed because of negative results obtained after screening fish CNS extracts with radioimmunassays for mammalian dynorphin-related products (Dores et al, 1993). However, the conclusions drawn from these earlier studies had to be tempered by the fact that substitutions in the putative fish dynorphin-related products could have altered the antigenic determinants of the putative fish dynorphins.…”

Section: Prodynorphinmentioning

confidence: 99%

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Analyzing the evolution of the opioid/orphanin gene family

Dores

Lecaude

Bauer

et al. 2002

Mass Spectrometry Reviews

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Advances in molecular biology have made it possible to rapidly obtain the amino acid sequence of neuropeptide precursors-either by cloning and sequencing the cDNA that encodes the precursor, or by reconstructing the arrangement of exons and introns in a neuropeptide-coding gene through genomic approaches. The databases generated from these molecular approaches have been used to design probes to identify the cells that express the gene, or to ascertain the rate of expression of the gene, and even to predict the post-translational modifications that can generate functional neuropeptides from a biologically inert precursor. Although the power of these approaches is substantial, it is appreciated that a gene sequence or an mRNA sequence reflects the potential products that may be assembled in a secretory cell. To understand the functional capabilities of the secretory cell, the molecular genetics approaches must be combined with procedures that actually characterize the end-products generated by the secretory cell. Recent advances in two-dimensional gel electrophoresis and mass spectrometry now make it possible to analyze neuropeptides from a relatively small amount of tissue. These procedures can reveal novel end-products, tissue-specific endoproteolytic cleavage events, and developmental shifts in post-translational processing schemes. A gene family that illustrates all of these processes and the advantages of combining genomics with proteomics is the opioid/orphanin gene family.

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“…The mammalian Proenk contains four copies of Met-enk, one of Leu-enk and two Met-enk extended (Met-enk-RF (YGGFMRF) and Met-enk-RGL (YGGFMR-GL)) [22]. Such an organisation has also been found with little variation in other vertebrates phyla (for a review see [23]). In invertebrates, the existence of an opioid precursor(s) is still unknown.…”

Section: Phylogeny Of Enkephalins In Leechesmentioning

confidence: 99%