Ligand-induced changes in surface mu-opioid receptor number: relationship to G protein activation?

摘要: In this study, we explored the relationship between regulation of surface mu-opioid receptor number, ligand-induced G protein activation (measured by [(35)]S]guanosine-5'-O-(3-thio)triphosphate (GTPgammaS) binding) and second messenger signaling inhibition cAMP accumulation). Etorphine two isomers cis-beta-hydroxy-3-methylfentanyl (RTI-1a RTI-1b), which were full agonists for signaling, caused approximately a 50% loss receptors after 1 h treatment. Fentanyl morphine inhibiting accumulation partial stimulating [(35)S]GTPgammaS binding internalization. Although both 80% as efficacious etorphine in binding, fentanyl induced 35% receptors, whereas only 10% loss. Additionally, long- short-term treatment with opioid antagonist naloxone increases receptors. Unexpectedly, weak buprenorphine one isomer (RTI-1d) also found to cause an increase Treatment pertussis toxin (PTX) diminished agonist-induced Furthermore, abilities internalization more impaired PTX than that etorphine. significantly enhanced number 18-h buprenorphine. The results study suggest disruption coupling affects ligand-regulated mu-receptor trafficking can vary greatly ability regulate