The endocannabinoid system in the baboon (Papio spp.) as a complex framework for developmental pharmacology

Iram P. Rodriguez-Sanchez, Josee Guindon, Marco Ruiz, M. Elizabeth Tejero, Gene Hubbard, Laura E. Martinez-de-Villarreal, Hugo A. Barrera-Saldaña, Edward J. Dick, Anthony G. Comuzzie, Natalia E. Schlabritz-Loutsevitch

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)23-30
Number of pages8
JournalNeurotoxicology and Teratology
Volume58
DOIs
StatePublished - Nov 1 2016
Externally publishedYes

Fingerprint

Endocannabinoids
Papio
Pharmacology
Cannabinoids
Genes
Cannabis
Polymorphism
Amino Acids
Enzymes
Monoacylglycerol Lipases
Complementary DNA
Untranslated Regions
Cannabinoid Receptors
Phosphorylation
Lipoprotein Lipase
Primates
Poisons
Polymerase chain reaction
Mixed Function Oxygenases
Clone Cells

Keywords

  • Development
  • Endocannabinoid system
  • Homology
  • Non-human primates
  • Pharmacology

ASJC Scopus subject areas

  • Toxicology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Rodriguez-Sanchez, I. P., Guindon, J., Ruiz, M., Tejero, M. E., Hubbard, G., Martinez-de-Villarreal, L. E., ... Schlabritz-Loutsevitch, N. E. (2016). The endocannabinoid system in the baboon (Papio spp.) as a complex framework for developmental pharmacology. Neurotoxicology and Teratology, 58, 23-30. https://doi.org/10.1016/j.ntt.2016.06.006

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 journalArticle

Rodriguez-Sanchez, IP, Guindon, J, Ruiz, M, Tejero, ME, Hubbard, G, Martinez-de-Villarreal, LE, Barrera-Saldaña, HA, Dick, EJ, Comuzzie, AG & Schlabritz-Loutsevitch, NE 2016, 'The endocannabinoid system in the baboon (Papio spp.) as a complex framework for developmental pharmacology', Neurotoxicology and Teratology, vol. 58, pp. 23-30. https://doi.org/10.1016/j.ntt.2016.06.006
Rodriguez-Sanchez IP, Guindon J, Ruiz M, Tejero ME, Hubbard G, Martinez-de-Villarreal LE et al. The endocannabinoid system in the baboon (Papio spp.) as a complex framework for developmental pharmacology. Neurotoxicology and Teratology. 2016 Nov 1;58:23-30. https://doi.org/10.1016/j.ntt.2016.06.006
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. / The endocannabinoid system in the baboon (Papio spp.) as a complex framework for developmental pharmacology. In: Neurotoxicology and Teratology. 2016 ; Vol. 58. pp. 23-30.
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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.",
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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.

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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.

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