Journal article
Opioid receptors from a lower vertebrate (Catostomus commersoni): Sequence, pharmacology, coupling to a G-protein-gated inward-rectifying potassium channel (GIRK1), and evolution
Proceedings of the National Academy of Sciences of the United States of America, Vol.94(15), pp.8214-8219
1997
Abstract
The molecular evolution of the opioid receptor family has been studied by isolating cDNAs that encode six distinct opioid receptor-like proteins from a lower vertebrate, the teleost fish Catostomus commersoni. One of these, which has been obtained in full-length form, encodes a 383-amino acid protein that exhibits greatest sequence similarity to mammalian μ-opioid receptors; the corresponding gene is expressed predominantly in brain and pituitary. Transfection of the teleost cDNA into HEK 293 cells resulted in the appearance of a receptor having high affinity for the μ-selective agonist [D-Ala2, MePhe4-Gly-ol5] enkephalin (DAMGO) (K(d) = 0.63±0.15 nM) and for the nonselective antagonist naloxone (K(d) = 3.1±1.3 nM). The receptor had negligible affinity for U50488 and [D-Pen2, D-Pen5] enkephalin (DP-DPE), which are κ- and δ-opioid receptor selective agonists, respectively. Stimulation of transfected cells with 1 μM DAMGO lowered forskolin-induced cAMP levels, an effect that could be reversed by naloxone. Experiments in Xenopus oocytes have demonstrated that the fish opioid receptor can, in an agonist-dependent fashion, activate a coexpressed mouse G-protein-gated inward-rectifying potassium channel (GIRK1). The identification of six distinct fish opioid receptor-like proteins suggests that additional mammalian opioid receptors remain to be identified at the molecular level. Furthermore, our data indicate that the μ-opioid receptor arose very early in evolution, perhaps before the appearance of vertebrates, and that the pharmacological and functional properties of this receptor have been conserved over a period of ≃400 million years implying that it fulfills an important physiological role.
Details
- Title
- Opioid receptors from a lower vertebrate (Catostomus commersoni): Sequence, pharmacology, coupling to a G-protein-gated inward-rectifying potassium channel (GIRK1), and evolution
- Authors
- M G Darlison (Author) - Universität Hamburg, GermanyF R Greten (Author) - Universität Hamburg, GermanyRobert J Harvey (Author) - Universität Hamburg, GermanyH J Kreienkamp (Author) - Universität Hamburg, GermanyT Stühmer (Author) - Universität Hamburg, GermanyH Zwiers (Author) - University of Calgary, CanadaK Lederis (Author) - University of Calgary, CanadaD Richter (Author) - Universität Hamburg, Germany
- Publication details
- Proceedings of the National Academy of Sciences of the United States of America, Vol.94(15), pp.8214-8219
- Publisher
- National Academy of Sciences
- Date published
- 1997
- DOI
- 10.1073/pnas.94.15.8214
- ISSN
- 0027-8424
- Organisation Unit
- School of Health; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99451286002621
- Output Type
- Journal article
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