Sturgeon orphanin: A molecular "Fossil" that
bridges the gap between the opioids and orphanin FQ/N
by
Danielson PB, Hoversten MT, Fitzpatrick M,
Schreck C, Akil H, Dores RM.
Department of Biological Sciences,
University of Denver,
Denver, CO 80210.
J Biol Chem 2001 Apr 4

ABSTRACT

The elucidation of the cDNA sequence for sturgeon proorphanin provides a unique window for interpreting the evolutionary history of the opioid/orphanin gene family. The molecular "fossil" status of this precursor can be seen in several ancestral sequence characteristics that point to its origin as a duplication of either a prodynorphin- or proenkephalin-like gene. The sturgeon proorphanin cDNA encodes a precursor protein of 194 residues and the orphanin heptadecapeptide itself binds not only the opioid receptor-like 1 (ORL1) receptor but also the classical (?, kappa, and delta) opioid receptors with near equal affinity. Allowing for this are several amino acid substitutions at key positions in the heptadecapeptide sequence, relative to its mammalian orthologs, which have been linked by amino acid scans and site-directed mutageneic studies to the exclusion of mammalian orphanin FQ/N from classic opioid ligands (i.e., F(1) to Y(1); L(14) to W(14)). The unique receptor binding profile of sturgeon orphanin not only provides insight into the evolutionary history of the opioid and opioid-related peptides but also provides an ideal context in which to investigate the underlying mechanisms by which novel and often divergent physiological functions arise in receptor-ligand systems.

Pain
LAAM
Morphine
Tramadol
Nociceptin
Pain ethics
Opiophobia
Endomorphins
Novelty and pain
Receptor subtypes
Nociceptin/histamine
Fentanyl and ketamine
Opioids, mood and cognition
Nociceptin/orphanin and dopamine
Nociceptin antagonists: aminoquinolones

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