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This heterologous desensitization characterized by an uncoupling of G proteins from DOR is neither associated with modifications in receptor number nor in their phosphorylation but involves several kinases [cAMP-dependent protein kinase (PKA), MAP kinases/ERK kinase 1 (MEK1) and phosphoinositide-3 kinase (PI3K)] that could phosphorylate signaling proteins (Xu et al., 2013)