Mu-opioid receptor down-regulation and tolerance are not equally dependent upon G-protein signaling.
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Gomes BA, Shen J, Stafford K, Patel M, Yoburn BC
Mu-opioid receptor down-regulation and tolerance are not equally dependent upon G-protein signaling.
Pharmacol Biochem Behav. 2002 May;72(1-2):273-8.
- PubMed ID
- 11900797 [ View in PubMed]
- Abstract
In the present study, the contribution of pertussis toxin (PTX)-sensitive G(i/o)-proteins to opioid tolerance and mu-opioid receptor down-regulation in the mouse were examined. Mice were injected once intracerebroventricularly and intrathecally with PTX (0.1 microg/site). Controls were treated with saline. On the 10th day following PTX treatment, continuous subcutaneous infusion of etorphine (150 or 200 microg/kg/day) or morphine (40 mg/kg/day+25 mg slow-release pellet) was begun. Control mice were implanted with inert placebo pellets. Pumps and pellets were removed 3 days later, and mice were tested for morphine analgesia or mu-opioid receptor density was determined in the whole brain, spinal cord, and midbrain. Both infusion doses of etorphine produced significant tolerance (ED50 shift=approximately 4-6-fold) and down-regulation of mu-opioid receptors (approximately 20-35%). Morphine treatment also produced significant tolerance (ED50 shift= approximately 5-8-fold), but no mu-opioid receptor down-regulation. PTX dramatically reduced the acute potency of morphine and blocked the further development of tolerance by both etorphine and morphine treatments. However, PTX had no effect on etorphine-induced mu-opioid receptor down-regulation in brain, cord, or midbrain. These results suggest that PTX-sensitive G-proteins have a minimal role in agonist-induced mu-opioid receptor density regulation in vivo, but are critical in mediating acute and chronic functional effects of opioids such as analgesia and tolerance.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Etorphine Mu-type opioid receptor Protein Humans YesAgonistDetails