Agonist-, antagonist-, and inverse agonist-regulated trafficking of the delta-opioid receptor correlates with, but does not require, G protein activation.

摘要: In this study, we explored the relationship between ligand-induced regulation of surface delta opioid receptors and G protein activation. activation was assessed with [(35)S]guanosine-5'-O-(3-thio)triphosphate (GTP gamma S) binding assays conducted at both 37 0 degrees C. Ligand-independent (constitutive) activity delta-receptor readily observed when [(35)S]GTP S assay performed We identified a new class alkaloid inverse agonists (RTI-5989-1, RTI-5989-23, RTI-5989-25), which are more potent than previously described peptide agonist ICI-174864 (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu). Treatment these for 18 h caused up-regulation receptors. Eighteen-hour treatment etorphine resulted in approximately 90% loss receptor, whereas fentanyl, diprenorphine, morphine 20 50% loss. The abilities ligands to modulate C showed strong correlation their regulate receptor number (r(2) = 0.86). Interestingly, ability fentanyl activate proteins markedly temperature sensitive. Fentanyl no stimulation but as efficacious etorphine, morphine, diprenorphine Neither increases nor decreases were perturbed by pertussis toxin pretreatment, suggesting that functional not required ligand-regulated delta-opioid trafficking.