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- W1723773923 abstract "Abstract The present study was designed to investigate the effect of repeated administration of a selective κ‐opioid receptor agonist (1 S ‐ trans )‐3,4‐dichloro‐ N ‐methyl‐ N ‐[2‐(1‐pyrrolidinyl)cyclohexyl]‐benzeneacetamide hydrochloride [(–)U‐50,488H] on antinociception and G‐protein activation induced by µ‐opioid receptor agonists in mice. A single s.c. injection of (–)U‐50,488H produced a dose‐dependent antinociception, and this effect was reversed by a selective κ‐opioid receptor antagonist nor‐binaltorphimine (nor‐BNI). Furthermore, a single s.c. pre‐treatment with (–)U‐50,488H had no effect on the µ‐opioid receptor agonist‐induced antinociception. In contrast, repeated s.c. administration of (–)U‐50,488H resulted in the development of tolerance to (–)U‐50,488H‐induced antinociception. Under these conditions, we demonstrated here that repeated s.c. injection of (–)U‐50,488H significantly enhanced the antinociceptive effect of selective µ‐opioid receptor agonists endomorphin‐1, endomorphin‐2 and [ d ‐Ala2, N ‐MePhe4,Gly‐ol5] enkephalin (DAMGO). Using the guanosine‐5′‐ o‐ (3‐[ 35 S]thio) triphosphate ([ 35 S]GTPγS) binding assay, we found that (–)U‐50,488H was able to produce a nor‐BNI‐reversible increase in [ 35 S]GTPγS binding to membranes of the mouse thalamus, which has a high level of κ‐opioid receptors. Repeated administration of (–)U‐50,488H caused a significant reduction in the (–)U‐50,488H‐stimulated [ 35 S]GTPγS binding in this region, whereas chronic treatment with (–)U‐50,488H exhibited the increase in the endomorphin‐1‐, endomorphin‐2‐ and DAMGO‐stimulated [ 35 S]GTPγS bindings in membranes of the thalamus and periaqueductal gray. These results suggest that repeated stimulation of κ‐opioid receptors leads to the heterologous up‐regulation of µ‐opioid receptor functions in the thalamus and periaqueductal gray regions, which may be associated with the supersensitivity of µ‐opioid receptor‐mediated antinociception." @default.
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- W1723773923 date "2003-05-14" @default.
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- W1723773923 title "Heterologous µ-opioid receptor adaptation by repeated stimulation of κ-opioid receptor: up-regulation of G-protein activation and antinociception" @default.
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- W1723773923 doi "https://doi.org/10.1046/j.1471-4159.2003.01754.x" @default.
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