Document Detail


CB(2) cannabinoid receptor antagonist SR144528 decreases mu-opioid receptor expression and activation in mouse brainstem: role of CB(2) receptor in pain.
MedLine Citation:
PMID:  18804501     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Formerly considered as an exclusively peripheral receptor, it is now accepted that CB(2) cannabinoid receptor is also present in limited amounts and distinct locations in the brain of several animal species, including mice. However, the possible roles of CB(2) receptors in the brain need to be clarified. The aim of our work was to study the mu-opioid receptor (MOR) mRNA expression level and functional activity after acute in vivo and in vitro treatments with the endocannabinoid noladin ether (NE) and with the CB(2) receptor antagonist SR144528 in brainstem of mice deficient in either CB(1) or CB(2) receptors. This study is based on our previous observations that noladin ether (NE) produces decrease in the activity of MOR in forebrain and this attenuation can be antagonized by the CB(2) cannabinoid antagonist SR144528, suggesting a CB(2) receptor mediated effect. We used quantitative real-time PCR to examine the changes of MOR mRNA levels, [(35)S]GTPgammaS binding assay to analyze the capability of mu-opioid agonist DAMGO to activate G-proteins and competition binding assays to directly measure the ligand binding to MOR in mice brainstem. After acute NE administration no significant changes were observed on MOR signaling. Nevertheless pretreatment of mice with SR144528 prior to the administration of NE significantly decreased MOR signaling suggesting the involvement of SR144528 in mediating the effect of MOR. mRNA expression of MORs significantly decreased both in CB(1) wild-type and CB(1) knockout mice after a single injection of SR144528 at 0.1mg/kg when compared to the vehicle treated controls. Consequently, MOR-mediated signaling was attenuated after acute in vivo treatment with SR144528 in both CB(1) wild-type and CB(1) knockout mice. In vitro addition of 1microM SR144528 caused a decrease in the maximal stimulation of DAMGO in [(35)S]GTPgammaS binding assays in CB(2) wild-type brainstem membranes whereas no significant changes were observed in CB(2) receptor knockouts. Radioligand binding competition studies showed that the noticed effect of SR144528 on MOR signaling is not mediated through MORs. Our data demonstrate that the SR144528 caused pronounced decrease in the activity of MOR is mediated via CB(2) cannabinoid receptors.
Authors:
Eszter Páldy; Erika Bereczki; Miklós Sántha; Tibor Wenger; Anna Borsodi; Andreas Zimmer; Sándor Benyhe
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-08-29
Journal Detail:
Title:  Neurochemistry international     Volume:  53     ISSN:  0197-0186     ISO Abbreviation:  Neurochem. Int.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-11-25     Completed Date:  2009-03-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8006959     Medline TA:  Neurochem Int     Country:  England    
Other Details:
Languages:  eng     Pagination:  309-16     Citation Subset:  IM    
Affiliation:
Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Temesvari krt. 62, H-6726 Szeged, Hungary.
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MeSH Terms
Descriptor/Qualifier:
Animals
Binding, Competitive / drug effects,  physiology
Bornanes / pharmacology*
Brain Stem / metabolism*
Down-Regulation / drug effects,  physiology
Endocannabinoids / agonists,  metabolism*
Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
Glycerides / pharmacology
Mice
Mice, Inbred C57BL
Mice, Knockout
Nociceptors / drug effects,  metabolism
Pain / metabolism*,  physiopathology
Pyrazoles / pharmacology*
RNA, Messenger / drug effects,  metabolism
Radioligand Assay
Receptor, Cannabinoid, CB1 / drug effects,  genetics
Receptor, Cannabinoid, CB2 / antagonists & inhibitors,  metabolism*
Receptors, Opioid, mu / genetics*
Chemical
Reg. No./Substance:
0/Bornanes; 0/Endocannabinoids; 0/Glycerides; 0/Pyrazoles; 0/RNA, Messenger; 0/Receptor, Cannabinoid, CB1; 0/Receptor, Cannabinoid, CB2; 0/Receptors, Opioid, mu; 0/SR 144528; 0/noladin ether; 100929-53-1/Enkephalin, Ala(2)-MePhe(4)-Gly(5)-

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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