uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Guineensine is a novel inhibitor of endocannabinoid uptake showing cannabimimetic behavioral effects in BALB/c mice
Show others and affiliations
2014 (English)In: Pharmacological Research, ISSN 1043-6618, E-ISSN 1096-1186, Vol. 80, 52-65 p.Article in journal (Refereed) Published
Abstract [en]

High-content screening led to the identification of the N-isobutylamide guineensine from Piper nigrum as novel nanomolar inhibitor (EC50= 290 nM) of cellular uptake of the endocannabinoid anandamide (AEA). Noteworthy, guineensine did not inhibit endocannabinoid degrading enzymes fatty acid amide hydrolase (FAAH) or monoacylglycerol lipase (MAGL) nor interact with cannabinoid receptors or fatty acid binding protein 5 (FABP5), a major cytoplasmic AEA carrier. Activity-based protein profiling showed no inhibition of serine hydrolases. Guineensine also inhibited the cellular uptake of 2-arachidonoylglycerol (2-AG). Preliminary structure-activity relationships between natural guineensine analogs indicate the importance of the alkyl chain length interconnecting the pharmacophoric isobutylamide and benzodioxol moieties for AEA cellular uptake inhibition. Guineensine dose-dependently induced cannabimimetic effects in BALB/c mice shown by strong catalepsy, hypothermia, reduced locomotion and analgesia. The catalepsy and analgesia were blocked by the CBI receptor antagonist rimonabant (SR141716A). Guineensine is a novel plant natural product which specifically inhibits endocannabinoid uptake in different cell lines independent of FAAH. Its scaffold may be useful to identify yet unknown targets involved in endocannabinoid transport.

Place, publisher, year, edition, pages
2014. Vol. 80, 52-65 p.
Keyword [en]
Guineensine, Anandamide uptake, Endocannabinoid transport inhibition, Cannabimimetic, Endocannabinoid system
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-221973DOI: 10.1016/j.phrs.2013.12.010ISI: 000332266000007OAI: oai:DiVA.org:uu-221973DiVA: diva2:710921
Available from: 2014-04-08 Created: 2014-04-07 Last updated: 2017-12-05

Open Access in DiVA

No full text

Other links

Publisher's full text

Authority records BETA

Blunder, Martina

Search in DiVA

By author/editor
Blunder, Martina
By organisation
Functional Pharmacology
In the same journal
Pharmacological Research
Neurosciences

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 426 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf