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Cannabinoid Ligand-Receptor Signaling During Early Pregnancy in the Mouse

  • Bibhash C. Paria
  • Sanjoy K. Das
  • Sudhansu K. Dey

Abstract

The recent identification and cloning of brain-type and spleen-type cannabinoid receptors (CB-1R and CB2-R, respectively) provide evidence that many of the effect of cannabinoids are mediated via these receptors. Using multiple appoaches (RT-PCR, Scatchard analysis, autoradiographic binding, cAMP assay, Western blotting, and immunocytochemistry), we demonstrated that functional CB1-R receptors are present in the preimplantation embryo and uterus. The levels of CB1-R in the embryo are much higher than those in the brain. Furthermore, the mouse uterus has the anandamide synthesizing and hydrolyzing capacities that are differentially regulated during the peri-implantation period. The uterus contains the highest levels of anandamide yet discovered in a mammalian tissue. These results suggest that preimplantation mouse embryos are possible targets for cannabinoid ligand-receptor signaling. Indeed, activation of embryonic cannabinoid receptors by natural and synthetic cannabinoid ligands interferes with preimplantaion embryo development, and this effect is completely reversed by a specific CB1-R antagonist. These results suggest that cannabinoid effects on embryo develpment are mediated by CB1-R We also observed that Δ9-tetrahydrocannabinol [(-)THC] infused in the presence of cytochrome P450 inhibitors interfered with blastocyst implantation. This adverse effect was reversed by coinfusion of CB1-R antagonist. Collectively, these results demonstrated that cannabinoid effects on embryo development and implantation are mediated by embryonic and/or uterine CB1-R.

Keywords

Preimplantation Embryo Mouse Uterus Amidase Activity Mouse Blastocyst Cytochrome P450 Inhibitor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Bibhash C. Paria
  • Sanjoy K. Das
  • Sudhansu K. Dey

There are no affiliations available

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