Logo image
Opioid receptors from a lower vertebrate (Catostomus commersoni): Sequence, pharmacology, coupling to a G-protein-gated inward-rectifying potassium channel (GIRK1), and evolution
Journal article   Peer reviewed

Opioid receptors from a lower vertebrate (Catostomus commersoni): Sequence, pharmacology, coupling to a G-protein-gated inward-rectifying potassium channel (GIRK1), and evolution

M G Darlison, F R Greten, Robert J Harvey, H J Kreienkamp, T Stühmer, H Zwiers, K Lederis and D Richter
Proceedings of the National Academy of Sciences of the United States of America, Vol.94(15), pp.8214-8219
1997
url
https://doi.org/10.1073/pnas.94.15.8214View
Published Version

Abstract

cDNA cloning functional expression peptide receptor teleost fish xenopus oocyte
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

Metrics

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Collaboration types
Domestic collaboration
International collaboration
Web Of Science research areas
Biochemistry & Molecular Biology

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

Source: InCites

Logo image