The endocannabinoid system in the baboon (Papio spp.) as a complex framework for developmental pharmacology.
The consumption of marijuana (exogenous cannabinoid) almost doubled in adults during last decade. Consumption of exogenous cannabinoids interferes with the endogenous cannabinoid (or "endocannabinoid" (eCB)) system (ECS), which comprises N-arachidonylethanolamide (anandamide, AEA), 2-arachidonoyl glycerol (2-AG), endocannabinoid receptors (cannabinoid receptors 1 and 2 (CB1R and CB2R), encoded by CNR1 and CNR2, respectively), and synthesizing/degrading enzymes (FAAH, fatty-acid amide hydrolase; MAGL, monoacylglycerol lipase; DAGL-α, diacylglycerol lipase-alpha). Reports regarding the toxic and therapeutic effects of pharmacological compounds targeting the ECS are sometimes contradictory. This may be caused by the fact that structure of the eCBs varies in the species studied.



First: to clone and characterize the cDNAs of selected members of ECS in a non-human primate (baboon, Papio spp.), and second: to compare those cDNA sequences to known human structural variants (single nucleotide polymorphisms and haplotypes).



Polymerase chain reaction-amplified gene products from baboon tissues were transformed into Escherichia coli. Amplicon-positive clones were sequenced, and the obtained sequences were conceptually translated into amino-acid sequences using the genetic code.



Among the ECS members, CNR1 was the best conserved gene between humans and baboons. The phenotypes associated with mutations in the untranslated regions of this gene in humans have not been described in baboons. One difference in the structure of CNR2 between humans and baboons was detected in the region with the only known clinically relevant polymorphism in a human receptor. All of the differences in the amino-acid structure of DAGL-α between humans and baboons were located in the hydroxylase domain, close to phosphorylation sites. None of the differences in the amino-acid structure of MAGL observed between baboons and humans were located in the area critical for enzyme function.



The evaluation of the data, obtained in non-human primate model of cannabis-related developmental exposure should take into consideration possible evolutionary-determined species-specific differences in the CB1R expression, CB2R transduction pathway, and FAAH and DAGLα substrate-enzyme interactions.
Universidad Autónoma de Nuevo León, Facultad de Medicina, Departamento de Genética, Monterrey, Nuevo León, Mexico.
Iram P
IP
Rodriguez-Sanchez
Department of Pharmacology and Neurobiology, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
Josee
J
Guindon
Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center at the Permian Basin, Odessa, TX, USA.
Marco
M
Ruiz
Laboratorio de Nutrigenética y Nutrigenómica, Instituto Nacional de Medicina Genómica (INMEGEN), México, D.F., Mexico.
M Elizabeth
ME
Tejero
Department of Pathology, University of Texas at San Antonio, San Antonio, TX, USA.
Gene
G
Hubbard
Universidad Autónoma de Nuevo León, Facultad de Medicina, Departamento de Genética, Monterrey, Nuevo León, Mexico.
Laura E
LE
Martinez-de-Villarreal
Universidad Autónoma de Nuevo León, Facultad de Medicina, Departamento de Bioquímica y Medicina Molecular, Monterrey, Nuevo León, Mexico.
Hugo A
HA
Barrera-Saldaña
Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.
Edward J
EJ
Dick
Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
Anthony G
AG
Comuzzie
Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center at the Permian Basin, Odessa, TX, USA. Electronic address: Natalia.schlabritz-lutsevich@ttuhsc.edu.
Natalia E
NE
Schlabritz-Loutsevitch
D000581:Amidohydrolases / Q000235:genetics; D000818:Animals; D063388:Endocannabinoids / Q000235:genetics*; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics; D008099:Liver / Q000378:metabolism; D023421:Models, Animal; D008994:Monoacylglycerol Lipases / Q000235:genetics; D010215:Papio; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics; D013045:Species Specificity; D057170:Translational Research, Biomedical; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D063388:Endocannabinoids; D008071:Lipoprotein Lipase; D008994:Monoacylglycerol Lipases; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D000099252:Fatty Acid Amide Hydrolases; C571130:CNR1 protein, human; C588309:CNR2 protein, human; C480280:DAGLA protein, human
Development; Endocannabinoid system; Homology; Non-human primates; Pharmacology