Abstract
Introduction 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. Objectives 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). Materials and methods 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. Results 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. Conclusion 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 23-30 |
| Number of pages | 8 |
| Journal | Neurotoxicology and Teratology |
| Volume | 58 |
| DOIs | |
| State | Published - Nov 1 2016 |
| Externally published | Yes |
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Keywords
- Development
- Endocannabinoid system
- Homology
- Non-human primates
- Pharmacology
ASJC Scopus subject areas
- Toxicology
- Developmental Neuroscience
- Cellular and Molecular Neuroscience
Cite this
The endocannabinoid system in the baboon (Papio spp.) as a complex framework for developmental pharmacology. / Rodriguez-Sanchez, Iram P.; Guindon, Josee; Ruiz, Marco; Tejero, M. Elizabeth; Hubbard, Gene; Martinez-de-Villarreal, Laura E.; Barrera-Saldaña, Hugo A.; Dick, Edward J.; Comuzzie, Anthony G.; Schlabritz-Loutsevitch, Natalia E.
In: Neurotoxicology and Teratology, Vol. 58, 01.11.2016, p. 23-30.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The endocannabinoid system in the baboon (Papio spp.) as a complex framework for developmental pharmacology
AU - Rodriguez-Sanchez, Iram P.
AU - Guindon, Josee
AU - Ruiz, Marco
AU - Tejero, M. Elizabeth
AU - Hubbard, Gene
AU - Martinez-de-Villarreal, Laura E.
AU - Barrera-Saldaña, Hugo A.
AU - Dick, Edward J.
AU - Comuzzie, Anthony G.
AU - Schlabritz-Loutsevitch, Natalia E.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - Introduction 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. Objectives 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). Materials and methods 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. Results 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. Conclusion 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.
AB - Introduction 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. Objectives 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). Materials and methods 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. Results 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. Conclusion 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.
KW - Development
KW - Endocannabinoid system
KW - Homology
KW - Non-human primates
KW - Pharmacology
UR - http://www.scopus.com/inward/record.url?scp=85001875277&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85001875277&partnerID=8YFLogxK
U2 - 10.1016/j.ntt.2016.06.006
DO - 10.1016/j.ntt.2016.06.006
M3 - Article
C2 - 27327781
AN - SCOPUS:85001875277
VL - 58
SP - 23
EP - 30
JO - Neurotoxicology and Teratology
JF - Neurotoxicology and Teratology
SN - 0892-0362
ER -