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On the cAMP pathway, U50,488 (trans-(±)-3,4-Dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide) and dynorphin A (1-17) produced a greater KOR desensitization than etorphine or levorphanol (Blake et al., With respect to desensitization, all those data support the idea that agonists are able to promote a different regulation of OR as demonstrated for other GPCR such as the histamine H2 receptors (Alonso et al., Mechanisms of OR desensitization OR phosphorylation Numerous studies have been carried out to demonstrate the role of OR phosphorylation in desensitization by using chemical inhibitors of kinases, in vitro or in vivo knock-out (KO) of kinases using siRNA or transgenic mice, over-expression of dominant negative mutants of kinases, amino acid substitution or truncation on OR