CB1 receptor-independent effects of the CB1 receptor antagonist/inverse agonist rimonabant (SR141716)

Abstract

Event Abstract Back to Event CB1 receptor-independent effects of the CB1 receptor antagonist/inverse agonist rimonabant (SR141716) Mária Szűcs1* and Resat Cinar1 1 Institute of Biochemistry, Biological Research Center, Hung. Acad. Sci., Hungary Growing body of evidences suggests that many G-protein coupled receptors (GPCRs) exhibit spontaneous activity in the absence of agonists which can be blocked by inverse agonists. The cannabinoid CB1 receptor antagonist SR141716 at high concentrations has been shown to inhibit basal G-protein activity by many investigators. However, it is still unclear whether this effect is mediated via CB1 receptors. Using the ligand-stimulated [35S]GTPγS assay that measures the initial step of any GPCR activation, we have found that SR141716 at micromolar concentrations significantly decreased the basal [35S]GTPγS binding in membranes of wild type and CB1 receptor knock-out mouse cortex and parental CHO cells, the latter not containing significant amount of the receptors tested. Thereby, it is concluded that the inverse agonist effect of SR141716 is CB1 receptor-independent. In CHO cells stably transfected with μ-opioid receptors, the specific μ-receptor agonist DAMGO resulted in 501 ± 29% stimulation over basal activity that was inhibited to 456 ± 22% by 10 μM SR141716. When the cells were pretreated with pertussis toxin (PTX) to uncouple the receptors from Gi/Go proteins, DAMGO had no significant effect by itself. Interestingly, combination of DAMGO and SR141716 resulted in 248 ± 21% stimulation over the basal activity which effect was completely inhibited by the prototypic opioid antagonist, naloxone. These results suggest the emergence of a novel, PTX-insensitive opioid signaling when the μ-receptors are activated by the combined presence of DAMGO and SR141716. It will require further studies to reveal the molecular mechanism of this effect. Conference: 12th Meeting of the Hungarian Neuroscience Society, Budapest, Hungary, 22 Jan - 24 Jan, 2009. Presentation Type: Poster Presentation Topic: Developmental neurobiology and subcortical functions Citation: Szűcs M and Cinar R (2009). CB1 receptor-independent effects of the CB1 receptor antagonist/inverse agonist rimonabant (SR141716). Front. Syst. Neurosci. Conference Abstract: 12th Meeting of the Hungarian Neuroscience Society. doi: 10.3389/conf.neuro.01.2009.04.242 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 13 Mar 2009; Published Online: 13 Mar 2009. * Correspondence: Mária Szűcs, Institute of Biochemistry, Biological Research Center, Hung. Acad. Sci., Szeged, Hungary, szucsm@brc.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Mária Szűcs Resat Cinar Google Mária Szűcs Resat Cinar Google Scholar Mária Szűcs Resat Cinar PubMed Mária Szűcs Resat Cinar Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.