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Novel pharmacology of putative cannabinoid targets and their ligands

The novel compound VSN16R was characterised and its functional effect in the central nervous system and periphery was investigated.  VSN16R behaved as an agonist in the mouse isolated vas deferens assay.  The functional effect of VSN16R appeared to involve GPR55 and GPR18 activation. The possibility that in addition to the CB<sub>1</sub> receptor; the CB<sub>2</sub> receptor, GPR55 and GPR18 contribute towards the effects of certain cannabinoid ligands in the nervous system (both central and peripheral) was investigated.  Results suggest that the cannabinoid CB<sub>2</sub> receptor and also GPR55 and GPR18 are functional in the mouse vas deferens. The results imply that in addition to the CB<sub>1</sub> receptor, the CB<sub>2</sub> receptor can mediate the effects of certain cannabinoids, including CP55940, AEA and Δ<sup>9</sup>-THC, but not JWH015 in the [<sup>35</sup>S]GTPγS assay with brain region membranes.  GPR55 can mediate the effects of certain cannabinoids, including CP55940 and JWH015 in the [<sup>35</sup>S]GTPγS assay with brain region membranes.  GPR55 was also shown to mediate the effect of JWH015, but  not O-1602 in the mouse isolated vas deferens assay, indicating an additional target for O-1602 in this tissue.  Data obtained suggest that CP55940 and AEA, but not Δ<sup>9</sup>-THC, O-1602 or JWH015 can activate GPR18. The effect of cannabinoid ligands and VSN16R on human neutrophil migration was investigated. The functional effect of a range of phytocannabinoids and the ligand N-arachichidonoyl glycine (NAGly) at the receptor GPR902 was investigated.  The findings implied that CBD, CBG and Δ<sup>9</sup>-THC acid may be able to interact with GPR92 to antagonise the GPR92 agonist lysophosphatidic acid.

Identiferoai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:531908
Date January 2010
CreatorsTanner, Carolyn
PublisherUniversity of Aberdeen
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Sourcehttp://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=158821

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