Cannabinoid Ligand-Receptor Signaling During Early Pregnancy in the Mouse

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 Δ 9 -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. 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.