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See Latest ArticlesCB receptor-independent actions of SR141716 on G-protein signaling; co-application with the micro-opioid agonist DAMGO unmasks novel, pertussis toxin-insensitive opioid signaling in MOR-CHO cells
Journal of Pharmacology and Experimental Therapeutics, 05/18/09
Cinar R et al. - These results suggest the emergence of novel, PTX-insensitive G-protein signaling that is blocked by naloxone when MORs are activated by of the combination DAMGO + SR141716.
Maria Szucs, 05/22/09
| SR141716 (Rimonabant), has been shown to exert a plethora of effects in a number of pathological conditions such as obesity, metabolic syndrome, drug addiction. These effects are mainly attributed to its antagonistic properties at the CB1 receptors. However, the evidence is increasing to show that Rimonabant may also behave as an inverse agonist when used at high doses in diseases such as diarrhea, emesis, neuronal damage, liver fibrosis. Our work has revealed that Rimonabant exerts multifaceted effects on G-protein signaling. It is demonstrated that its inverse agonist effect, which is manifested at micromolar concentrations, is CB1 receptor-independent. Moreover, it may bind directly to mu-opioid receptors and influence their signaling, even resulting in the emergence of novel, opioid receptor-mediated G-protein activation in the combined presence with a mu-receptor agonist. It is anticipated that Rimonabant may also affect the signaling of other G-protein coupled receptors. The multifaceted actions of the drug should be taken into account when applied in high doses. |
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