Ligand-directed signalling within the opioid receptor family

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Ligand-directed signalling within the opioid receptor family.

The classic model of GPCR activation proposed that all agonists induce the same active receptor conformation. However, research over the last decade has shown that GPCRs exist in multiple conformations, and that agonists can stabilize different active states. The distinct receptor conformations induced by ligands result in distinct receptor-effector complexes, which produce varying levels of ac...

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Ligand bias refers to the ability of a drug at a receptor to activate selectively particular cell signalling pathways over others, in a way that cannot be explained by traditional models of receptor theory. For a physiologically and therapeutically important GPCR (G-protein-coupled receptor) such as the MOPr (μ-opioid receptor), the role of ligand bias is currently being explored, not only in o...

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Ligand-directed trafficking of the δ-opioid receptor in vivo: two paths toward analgesic tolerance.

δ-Opioid receptors are G-protein-coupled receptors that regulate nociceptive and emotional responses. It has been well established that distinct agonists acting at the same G-protein-coupled receptor can engage different signaling or regulatory responses. This concept, known as biased agonism, has important biological and therapeutic implications. Ligand-biased responses are well described in c...

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Ligand-directed signaling has been suggested as a basis for the differences in responses evoked by otherwise receptor-selective agonists. The underlying mechanisms are not understood, yet clearer definition of this concept may be helpful in the development of novel, pathway-selective therapeutic agents. We previously showed that kappa-opioid receptor activation of JNK by one class of ligand, bu...

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ژورنال

عنوان ژورنال: British Journal of Pharmacology

سال: 2012

ISSN: 0007-1188

DOI: 10.1111/j.1476-5381.2012.02075.x