Even L

References (2)

Title : Selective blockade of the hydrolysis of the endocannabinoid 2-arachidonoylglycerol impairs learning and memory performance while producing antinociceptive activity in rodents - Griebel_2015_Sci.Rep_5_7642
Author(s) : Griebel G , Pichat P , Beeske S , Leroy T , Redon N , Jacquet A , Francon D , Bert L , Even L , Lopez-Grancha M , Tolstykh T , Sun F , Yu Q , Brittain S , Arlt H , He T , Zhang B , Wiederschain D , Bertrand T , Houtmann J , Rak A , Vallee F , Michot N , Auge F , Menet V , Bergis OE , George P , Avenet P , Mikol V , Didier M , Escoubet J
Ref : Sci Rep , 5 :7642 , 2015
Abstract : Monoacylglycerol lipase (MAGL) represents a primary degradation enzyme of the endogenous cannabinoid (eCB), 2-arachidonoyglycerol (2-AG). This study reports a potent covalent MAGL inhibitor, SAR127303. The compound behaves as a selective and competitive inhibitor of mouse and human MAGL, which potently elevates hippocampal levels of 2-AG in mice. In vivo, SAR127303 produces antinociceptive effects in assays of inflammatory and visceral pain. In addition, the drug alters learning performance in several assays related to episodic, working and spatial memory. Moreover, long term potentiation (LTP) of CA1 synaptic transmission and acetylcholine release in the hippocampus, two hallmarks of memory function, are both decreased by SAR127303. Although inactive in acute seizure tests, repeated administration of SAR127303 delays the acquisition and decreases kindled seizures in mice, indicating that the drug slows down epileptogenesis, a finding deserving further investigation to evaluate the potential of MAGL inhibitors as antiepileptics. However, the observation that 2-AG hydrolysis blockade alters learning and memory performance, suggests that such drugs may have limited value as therapeutic agents.
ESTHER : Griebel_2015_Sci.Rep_5_7642
PubMedSearch : Griebel_2015_Sci.Rep_5_7642
PubMedID: 25560837
Gene_locus related to this paper: mouse-ABHD6

Title : Modified properties of serum cholinesterases in primary carcinomas - Zakut_1988_Cancer_61_727
Author(s) : Zakut H , Even L , Birkenfeld S , Malinger G , Zisling R , Soreq H
Ref : Cancer , 61 :727 , 1988
Abstract : Cholinesterases were characterized in the serum of 77 treated and 11 untreated patients having primary carcinomas of various tissue origins and 21 healthy volunteers which served as controls. In most of the samples, pseudocholinesterase (BCHE) accounted for almost all cholinesterase (ChE) activity and was inhibited by the organophosphorous poison tetraisopropyl pyrophosphoramide (iso-OMPA). In samples from the tumor-bearing patients, ChE degraded 733 +/- 59 nmole acetylcholine/h/mg protein, lower than the 960 +/- 175 nmole/hour/mg levels measured in controls. Tumor serum ChE exhibited elevated sensitivity to 1,5-bis-(4-allyldimethyl ammonium phenyl)-pentan-3-one dibromide (BW), the selective bisquaternary inhibitor of "true" acetylcholinesterase (AChE), with no correlation to age, sex, staging of tumor, presence of metastases or the specific treatment protocol, and with a different distribution pattern from the decrease in ChE specific activity or the sensitivity to iso-OMPA. In sucrose gradients, ChE sedimented as 12S in controls whereas in tumor serum samples from treated patients an additional component of 6 to 7 S, inhibited by both iso-OMPA and BW, also was detected. However, the ChE activity in serum of patients with diagnosed carcinomas before surgery and medical treatment appeared to be nondistinguishable from controls. These findings suggest that the modified properties of serum cholinesterases in carcinoma patients are not the result of the tumor itself, but that the common therapy protocols used in the treatment of primary carcinomas may cause the appearance of soluble ChE activity with properties of both AChE and BCHE, which accumulates in the serum.
ESTHER : Zakut_1988_Cancer_61_727
PubMedSearch : Zakut_1988_Cancer_61_727
PubMedID: 3338035