Eseménynaptár

Részletek

G protein-coupled receptors (GPCRs) mediate the majority of cellular responses to hormones and neurotransmitters, as well as the senses of sight, smell and taste. They represent the largest class of drug targets for the pharmaceutical industry; however, there are many obstacles to the discovery and development of safe and effective drugs for specific GPCR targets. I will provide an overview of the molecular basis of GPCR signaling, and discuss the challenges in drug discovery for GPCRs using the µ-opioid receptor (µOR) as a model system. The management of acute and chronic pain is one of the greatest challenges in modern medicine. While effective, many of the currently used opioid analgesics are highly addictive and their increased clinical use over the past 20 years is partially responsible for the opioid epidemic. The properties of more recently discovered µOR agonists suggest that it may be possible to separate analgesia from liabilities including addiction, tolerance and respiratory suppression. The µOR can signal through six G protein isoforms (Gi1,2,3, GoA,B, Gz), and through arrestin 2 and 3. We have observed that different µOR agonists differentially activate these signaling pathways. I will discuss what we have learned about the structural basis for G protein isoform and arrestin-biased signaling by the µOR.

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