Skip to main content

Research Repository

Advanced Search

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

Darlison, Mark G.; Greten, Florian R.; Harvey, Robert J.; Kreienkamp, Hans-J�rgen; St�hmer, Thorsten; Zwiers, Henk; Lederis, Karl; Richter, Dietmar

Authors

Mark G. Darlison

Florian R. Greten

Robert J. Harvey

Hans-J�rgen Kreienkamp

Thorsten St�hmer

Henk Zwiers

Karl Lederis

Dietmar Richter



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) (Kd = 0.63 ± 0.15 nM) and for the nonselective antagonist naloxone (Kd = 3.1 ± 1.3 nM). The receptor had negligible affinity for U50488 and [d-Pen2, d-Pen5]enkephalin (DPDPE), 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.

Citation

Darlison, M. G., Greten, F. R., Harvey, R. J., Kreienkamp, H., Stühmer, T., Zwiers, H., …Richter, D. (1997). 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, 94(15), 8214-8219

Journal Article Type Article
Acceptance Date May 29, 1997
Online Publication Date Jul 22, 1997
Publication Date 1997
Deposit Date Jul 26, 2016
Journal Proceedings of the National Academy of Sciences
Publisher National Academy of Sciences
Peer Reviewed Peer Reviewed
Volume 94
Issue 15
Pages 8214-8219
Public URL http://researchrepository.napier.ac.uk/Output/316317






Downloadable Citations