dc.contributor.author |
Patel Monica |
en |
dc.contributor.author |
Manning Jamie J |
en |
dc.contributor.author |
Finlay David B |
en |
dc.contributor.author |
Javitch Jonathan A |
en |
dc.contributor.author |
Banister Samuel D |
en |
dc.contributor.author |
Grimsey Natasha L |
en |
dc.contributor.author |
Glass Michelle |
en |
dc.date.accessioned |
2020-10-20T02:18:44Z |
|
dc.date.available |
2020-10-20T02:18:44Z |
|
dc.date.issued |
2020-5 |
en |
dc.identifier.issn |
0006-2952 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/53377 |
|
dc.description.abstract |
Synthetic cannabinoid receptor agonists (SCRAs) represent the most rapidly proliferating class of "designer drugs" or "new psychoactive substances". SCRAs offer unregulated alternatives to cannabis that evade routine drug tests, but their use is increasingly associated with severe toxicity and death worldwide. Little is currently known about SCRA molecular pharmacology, or the mechanisms underpinning their toxicity, although the effects are believed to be primarily mediated by the type 1 cannabinoid receptor (CB1). In this study, we aimed to characterise the signalling profiles of a structurally diverse panel of novel SCRAs at CB1. We compare SCRAs to traditional reference cannabinoids CP55,940, WIN55,212-2, and THC. The activity of the SCRAs was assessed in key receptor signalling and regulatory pathways, including cAMP production, translocation of β-arrestin 1 and 2, and receptor internalisation. The activity profiles of the ligands were also evaluated using operational analysis to identify ligand bias. Results revealed that SCRAs activities were relatively balanced in the pathways evaluated (compared to WIN55,212-2), although 5F-CUMYL-P7AICA and XLR-11 possessed partial efficacy in cAMP stimulation and β-arrestin translocation. Notably, the SCRAs showed distinct potency and efficacy profiles compared to THC. In particular, while the majority of SCRAs demonstrated robust β-arrestin translocation, cAMP stimulation, and internalisation, THC failed to elicit high efficacy responses in any of these assays. Further study is required to delineate if these pathways could contribute to SCRA toxicity in humans. |
en |
dc.format.medium |
Print-Electronic |
en |
dc.language |
eng |
en |
dc.publisher |
PERGAMON-ELSEVIER SCIENCE LTD |
en |
dc.relation.ispartofseries |
Biochemical pharmacology |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
1115 Pharmacology and Pharmaceutical Sciences |
en |
dc.subject |
Biomedical |
en |
dc.subject |
Basic Science |
en |
dc.subject |
Cannabinoid Research |
en |
dc.subject |
Substance Abuse |
en |
dc.subject |
Drug Abuse (NIDA only) |
en |
dc.subject |
Generic Health Relevance |
en |
dc.subject |
Science & Technology |
en |
dc.subject |
Life Sciences & Biomedicine |
en |
dc.subject |
Pharmacology & Pharmacy |
en |
dc.subject |
Synthetic cannabinoid receptor agonist |
en |
dc.subject |
Cannabinoid receptor |
en |
dc.subject |
Ligand bias |
en |
dc.subject |
THC |
en |
dc.subject |
beta-Arrestin |
en |
dc.subject |
CELL-CULTURE MODEL |
en |
dc.subject |
MU-OPIOID RECEPTOR |
en |
dc.subject |
PHARMACOLOGICAL EVALUATION |
en |
dc.subject |
BIASED AGONISM |
en |
dc.subject |
HEK293T CELLS |
en |
dc.subject |
AB-CHMINACA |
en |
dc.subject |
CB1 |
en |
dc.subject |
INTERNALIZATION |
en |
dc.subject |
LIGANDS |
en |
dc.subject |
SPICE |
en |
dc.subject |
1115 Pharmacology And Pharmaceutical Sciences |
en |
dc.title |
Signalling profiles of a structurally diverse panel of synthetic cannabinoid receptor agonists. |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1016/j.bcp.2020.113871 |
en |
pubs.begin-page |
113871 |
en |
pubs.volume |
175 |
en |
dc.date.updated |
2020-09-08T04:38:49Z |
en |
dc.rights.holder |
Copyright: The author |
en |
pubs.author-url |
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000527350300016&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=6e41486220adb198d0efde5a3b153e7d |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Journal Article |
en |
pubs.elements-id |
796160 |
en |
dc.identifier.eissn |
1873-2968 |
en |
pubs.number |
UNSP 113871 |
en |