Opioid desensitization/tolerance mechanisms have largely focused on adaptations that occur on the level of the @entity6253 ( @entity6253 ) itself. These include opioid receptor phosphorylation and ensuing trafficking events. Recent research, however, has revealed additional adaptations that occur downstream from the opioid receptor, which involve covalent modification of signaling molecules and altered associations among them. These include augmented isoform-specific synthesis of adenylyl cyclase (AC) and their phosphorylation as well as augmented phosphorylation of the G(beta) subunit of G(beta gamma). The aggregate effect of these changes is to shift @entity6253 -coupled signaling from predominantly G(i alpha) inhibitory to (G(i)-derived) G(beta gamma) stimulatory AC signaling. Most recently, chronic @entity1286 has been shown to enhance the association (interaction) between @entity6253 and G(s), which should provide an additional avenue for offsetting inhibitory @entity6253 signaling sequelae. The unfolding complexity of chronic @entity1286 -induced sequelae demands an evolving broader and more encompassing perspective on opioid tolerance-producing mechanisms. This should facilitate understanding tolerance within the context of physiological plasticity that is activated by chronic exposure to drugs of abuse. Additional research is required to integrate the various tolerance-producing adaptations that have been elucidated to date. Specifically, the relative contribution to opioid tolerance of identified adaptations is still unknown as is the extent to which they vary among different regions of the central nervous system.

Post-opioid receptor adaptations to chronic XXXX ; altered functionality and associations of signaling molecules.

@entity6253 :: ('4988', 'Gene') :: ['mu-opioid receptor', 'MOR'] @entity1286 :: ('MESH:D009020', 'Chemical') :: ['morphine']
@entity1286 :: (MESH:D009020,Chemical) :: ['morphine']
