We have studied how methadone, a potent opiate analgesic commonly used in the treatment of heroin addiction, inhibits cAMP accumulation by its interaction with the recently cloned rat μ opioid receptor. We have measured cAMP levels in Chinese hamster ovary (CHO) cells that stably expressed the μ receptor cDNA. When these cells were stimulated with 10 μM forskolin, methadone was able to inhibit the accumulation of cAMP with an IC50 of 28.3 nM. Moreover, methadone's inhibition of cAMP production was reversible by naloxone and was pertussis toxin sensitive. These findings are consistent with the interpretation that methadone binding to the μ opioid receptor is coupled to the activation of a Gi/Go protein.
ASJC Scopus subject areas
- Clinical Biochemistry
- Cellular and Molecular Neuroscience