Characterization of zebrafish proenkephalin reveals novel opioid sequences

Núñez, Verónica; González-Sarmiento, Rogelio; Rodrı́guez, Raquel E.

doi:10.1016/s0169-328x(03)00126-8

Cited by 46 publications

(13 citation statements)

References 48 publications

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“…The zebrafish genome is the only sequenced teleost genome with a duplicate of this gene. The gene located on zebrafish chromosome 7 ( PENKa ) has an insertion between the two first core sequences and is missing the third core sequence, while the gene on chromosome 2 ( PENKb ) does not have this insertion and has retained the third core sequence, but has a degenerate sixth core sequence, as described earlier [25], [26]. The zebrafish duplicates presumably resulted from of the teleost-specific whole genome duplication, hence we have named them PENKa and PENKb .…”

Section: Resultsmentioning

confidence: 93%

Concomitant Duplications of Opioid Peptide and Receptor Genes before the Origin of Jawed Vertebrates

2010

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BackgroundThe opioid system is involved in reward and pain mechanisms and consists in mammals of four receptors and several peptides. The peptides are derived from four prepropeptide genes, PENK, PDYN, PNOC and POMC, encoding enkephalins, dynorphins, orphanin/nociceptin and beta-endorphin, respectively. Previously we have described how two rounds of genome doubling (2R) before the origin of jawed vertebrates formed the receptor family.Methodology/Principal FindingsOpioid peptide gene family members were investigated using a combination of sequence-based phylogeny and chromosomal locations of the peptide genes in various vertebrates. Several adjacent gene families were investigated similarly. The results show that the ancestral peptide gene gave rise to two additional copies in the genome doublings. The fourth member was generated by a local gene duplication, as the genes encoding POMC and PNOC are located on the same chromosome in the chicken genome and all three teleost genomes that we have studied. A translocation has disrupted this synteny in mammals. The PDYN gene seems to have been lost in chicken, but not in zebra finch. Duplicates of some peptide genes have arisen in the teleost fishes. Within the prepropeptide precursors, peptides have been lost or gained in different lineages.Conclusions/SignificanceThe ancestral peptide and receptor genes were located on the same chromosome and were thus duplicated concomitantly. However, subsequently genetic linkage has been lost. In conclusion, the system of opioid peptides and receptors was largely formed by the genome doublings that took place early in vertebrate evolution.

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Section: Resultsmentioning

confidence: 93%

Concomitant Duplications of Opioid Peptide and Receptor Genes before the Origin of Jawed Vertebrates

2010

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“…Zebrafi sh PENK codes for a polypeptide of 249 residues with the consensus sequences for four Met-enkephalins (ME), one Leu-enkephalin (LE), and one Met-enkephalin-Gly-Tyr (MEGY 1 ) (Figure 1; Gonzalez-Nunez et al 2003a). The MEGY heptapeptide is present in two different evolutionary lineages of fi sh (actinopterigian and sarcopterigian fi sh), which share a common ancestor with tetrapods; thus this peptide appeared early in evolution and later evolved to Met-enkephalin-Arg-Phe (MERF) in tetrapods (Gonzalez-Nunez et al 2003a).…”

Section: Drpenkmentioning

confidence: 99%

“…The MEGY heptapeptide is present in two different evolutionary lineages of fi sh (actinopterigian and sarcopterigian fi sh), which share a common ancestor with tetrapods; thus this peptide appeared early in evolution and later evolved to Met-enkephalin-Arg-Phe (MERF) in tetrapods (Gonzalez-Nunez et al 2003a).…”

Section: Drpenkmentioning

confidence: 99%

The Zebrafish: A Model to Study the Endogenous Mechanisms of Pain

González-Núñez¹,

Rodrı́guez²

2009

ILAR Journal

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The difficulty of designing new analgesic drugs is evident in the biochemical maze that results when an opioid agonist binds to opioid receptors, triggering a complex cascade of intracellular mechanisms. In an effort to enhance understanding of the biochemical and pharmacological mechanisms that are responsible for the action of opioid drugs, we describe the characterization of the zebrafish opioid system, a novel experimental approach to unravel the molecular mechanisms that underlie opioid activity. We have cloned the zebrafish opioid receptors and peptides, established their expression pattern during development and in the adult organism, and determined their pharmacological profiles and biochemical properties. Furthermore, developmental studies in the zebrafish yield valuable information about the developmental roles of the opioid receptors. Building on these findings, we show that the zebrafish opioid receptors and peptides present molecular, pharmacological, and biochemical profiles that are fundamentally similar to those of their mammalian counterparts and from which results can therefore be extrapolated to higher vertebrates. Thus the zebrafish represents a straightforward model to study opioid activity, and can be very useful not only for the analysis of the complex endogenous systems that regulate the action of opioid agents but also for in vivo tests of novel analgesic drugs.

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“…Interestingly, in amphibians, Leu-enkephalin sequence is present in prodynorphin gene instead of proenkephalin gene [12]. On the other hand, the fish proenkephalin contains both methionine-enkephalin and Leucine-enkephalin as comparable to mammals [9].…”

Section: Introductionmentioning

confidence: 99%