Contrasting effects of μ opioid receptor and δ opioid receptor deletion upon the behavioral and neurochemical effects of cocaine

Neuroscience ◽  
2004 ◽  
Vol 127 (2) ◽  
pp. 497-503 ◽  
Author(s):  
V.I. Chefer ◽  
B.L. Kieffer ◽  
T.S. Shippenberg
2001 ◽  
Vol 276 (15) ◽  
pp. 12345-12355 ◽  
Author(s):  
Kirti Chaturvedi ◽  
Persis Bandari ◽  
Norihiro Chinen ◽  
Richard D. Howells

This study investigated the mechanism of agonist-induced opioid receptor down-regulation. Incubation of HEK 293 cells expressing FLAG-tagged δ and μ receptors with agonists caused a time-dependent decrease in opioid receptor levels assayed by immunoblotting. Pulse-chase experiments using [35S]methionine metabolic labeling indicated that the turnover rate of δ receptors was accelerated 5-fold following agonist stimulation. Inactivation of functional Giand Goproteins by pertussis toxin-attenuated down-regulation of the μ opioid receptor, while down-regulation of the δ opioid receptor was unaffected. Pretreatment of cells with inhibitors of lysosomal proteases, calpain, and caspases had little effect on μ and δ opioid receptor down-regulation. In marked contrast, pretreatment with proteasome inhibitors attenuated agonist-induced μ and δ receptor down-regulation. In addition, incubation of cells with proteasome inhibitors in the absence of agonists increased steady-state μ and δ opioid receptor levels. Immunoprecipitation of μ and δ opioid receptors followed by immunoblotting with ubiquitin antibodies suggested that preincubation with proteasome inhibitors promoted accumulation of polyubiquitinated receptors. These data provide evidence that the ubiquitin/proteasome pathway plays a role in agonist-induced down-regulation and basal turnover of opioid receptors.


2003 ◽  
Vol 23 (12) ◽  
pp. 4888-4898 ◽  
Author(s):  
Anne Morinville ◽  
Catherine M. Cahill ◽  
M. James Esdaile ◽  
Haneen Aibak ◽  
Brian Collier ◽  
...  

2000 ◽  
Vol 397 (1) ◽  
pp. 227
Author(s):  
Chunyuan Qiu ◽  
Ichiro Sora ◽  
Ke Ren ◽  
George Uhl ◽  
Ronald Dubner

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