The human mu opioid receptor: modulation of functional desensitization by calcium/calmodulin-dependent protein kinase and protein kinase C

• DOI: 10.1523/jneurosci.15-03-02396.1995
• Publication Date: 2018-04-06T16:05:41Z
• Authors: A Mestek; JH Hurley; LS Bye; AD Campbell; Y Chen; M Tian; J Liu; H Schulman; L Yu
• Keywords: μ-opioid receptor; Homologous desensitization

Opioids are some of the most efficacious analgesics used in humans. Prolonged administration opioids, however, often causes development drug tolerance, thus limiting their effectiveness. To explore molecular basis those mechanisms that may contribute to opioid we have isolated a cDNA for human mu receptor, target such narcotics as morphine, codeine, methadone, and fentanyl. The receptor encoded by this is 400 amino acids long with 94% sequence similarity rat receptor. Transient expression COS-7 cells produced high-affinity binding sites mu-selective agonists antagonists. This displays functional coupling recently cloned G-protein-activated K+ channel. When both proteins were expressed Xenopus oocytes, desensitization developed upon repeated stimulation observed reduction current induced second activation relative first. extent was potentiated multifunctional calcium/calmodulin-dependent protein kinase C. These results demonstrate modulation mechanism which signaling be regulated at cellular level, suggesting tolerance