Specific activation of the μ opioid receptor (MOR) by endomorphin 1 and endomorphin 2

Krisztina Monory, Marie Claude Bourin, Mariana Spetea, Csaba Tömböly, Géza Tóth, Hans W. Matthes, Brigitte L. Kieffer, Jacques Hanoune, Anna Borsodi

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Abstract

The recently discovered endomorphin 1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin 2 (Tyr-Pro-Phe-Phe-NH2) were investigated with respect to their direct receptor-binding properties, and to their ability to activate G proteins and to inhibit adenylyl cyclase in both cellular and animal models. Both tetrapeptides activated G proteins and inhibited adenylyl cyclase activity in membrane preparations from cells stably expressing the μ opioid receptor, an effect reversed by the μ receptor antagonist CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2), but they had no influence on cells stably expressing the δ opioid receptor. To further establish the selectivity of these peptides for the μ opioid receptor, brain preparations of mice lacking the μ opioid receptor gene were used to study their binding and signalling properties. Endomorphin 2, tritiated by a dehalotritiation method resulting in a specific radioactivity of 1.98 TBq/mmol (53.4 Ci/mmol), labelled the brain membranes of wild-type mice with a K(d) value of 1.77 nM and a B(max) of 63.33 fmol/mg protein. In membranes of mice lacking the μreceptor gene, no binding was observed, and both endomorphins failed to stimulate [35S]guanosine-5'-O-(3-thio)triphosphate ([35S]GTPγS) binding and to inhibit adenylyl cyclase. These data show that endomorphins are capable of activating G proteins and inhibiting adenylyl cyclase activity, and all these effects are mediated by the μ opioid receptors.

Original languageEnglish
Pages (from-to)577-584
Number of pages8
JournalEuropean Journal of Neuroscience
Volume12
Issue number2
DOIs
Publication statusPublished - Mar 22 2000

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Keywords

  • Adenylyl cyclase
  • Endogenous opioid peptides
  • In vitro radioligand binding
  • Knockout mice
  • [S]GTPγS binding

ASJC Scopus subject areas

  • Neuroscience(all)

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