In vivo opioid receptor heteromerization: where do we stand?

作者：Massotte D

来源：British Journal of Pharmacology, 2015, 172(2): 420-434.

DOI：10.1111/bph.12702

• opioid receptors
• GPCRs
• heteromer
• nociception
• mood disorders
• addiction
• fluorescent knock-in mice

Opioid receptors are highly homologous GPCRs that modulate brain function at all levels of neural integration, including autonomous, sensory, emotional and cognitive processing. Opioid receptors functionally interact in vivo, but the underlying mechanisms involving direct receptor-receptor interactions, affecting signalling pathways or engaging different neuronal circuits, remain unsolved. Heteromer formation through direct physical interaction between two opioid receptors or between an opioid receptor and a non-opioid one has been postulated and can be characterized by specific ligand binding, receptor signalling and trafficking properties. However, despite numerous studies in heterologous systems, evidence for physical proximity in vivo is only available for a limited number of opioid heteromers, and their physiopathological implication remains largely unknown mostly due to the lack of appropriate tools. Nonetheless, data collected so far using endogenous receptors point to a crucial role for opioid heteromers as a molecular entity that could underlie human pathologies such as alcoholism, acute or chronic pain as well as psychiatric disorders. Opioid heteromers therefore stand as new therapeutic targets for the drug discovery field.
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• 出版日期2015-1