| Title : Brain regional cannabinoid CB1 receptor signalling and alternative enzymatic pathways for 2-arachidonoylglycerol generation in brain sections of diacylglycerol lipase deficient mice - Aaltonen_2014_Eur.J.Pharm.Sci_51_87 |
| Author(s) : Aaltonen N , Riera Ribas C , Lehtonen M , Savinainen JR , Laitinen JT |
| Ref : Eur J Pharm Sci , 51 :87 , 2014 |
| Abstract : Endocannabinoids are the endogenous ligands of the G protein-coupled cannabinoid receptors. The principal brain endocannabinoid, 2-arachidonoylglycerol (2-AG), is enzymatically produced by postsynaptic neurons and then activates presynaptic CB1 receptors in a retrograde manner. The primary pathway for 2-AG generation is believed to be conversion from the diacylglycerols (DAGs) by two sn-1-specific lipases, DAGLalpha and DAGLbeta. Previous studies with DAGL-deficient mice indicated that DAGLalpha is the major enzyme needed for retrograde synaptic 2-AG signalling. The current study investigated whether the CB1 receptor-mediated Gi/o protein activity is altered in brain cryosections of DAGL-deficient mice when compared to wild-type mice and whether the sn-1-specific DAGLs are able to generate 2-AG in brain cryosections. Functional autoradiography indicated that brain regional CB1 receptor-Gi/o-activity largely remained unaltered in DAGLalpha-knockout and DAGLbeta-knockout mice when compared to wild-type littermates. Following comprehensive pharmacological blockade of 2-AG hydrolysis, brain sections generated sufficient amounts of 2-AG to activate CB1 receptors throughout the regions endowed with these receptors. As demonstrated by LC/MS/MS, this pool of 2-AG was generated via tetrahydrolipstatin-sensitive enzymatic pathways distinct from DAGLalpha or DAGLbeta. We conclude that in addition to the sn-1-specific DAGLs, additional 2-AG generating enzymatic pathways are active in brain sections. |
| ESTHER : Aaltonen_2014_Eur.J.Pharm.Sci_51_87 |
| PubMedSearch : Aaltonen_2014_Eur.J.Pharm.Sci_51_87 |
| PubMedID: 24012970 |
Aaltonen N, Riera Ribas C, Lehtonen M, Savinainen JR, Laitinen JT (2014)
Brain regional cannabinoid CB1 receptor signalling and alternative enzymatic pathways for 2-arachidonoylglycerol generation in brain sections of diacylglycerol lipase deficient mice
Eur J Pharm Sci
51 :87
Aaltonen N, Riera Ribas C, Lehtonen M, Savinainen JR, Laitinen JT (2014)
Eur J Pharm Sci
51 :87