Tuning the oviduct to the anandamide tone.
Anandamide (N-arachidonoylethanolamide) is a lipid signal molecule that was the first endogenous agonist for cannabinoid receptors to be discovered. Cannabinoid receptor type 1 (CB1) is widely distributed in neurons and nonneuronal cells in brain and peripheral organs including sperm, eggs, and preimplantation embryos. A study by Wang and colleagues in this issue of the JCI demonstrates that a critical balance between anandamide synthesis by N-acylphosphatidylethanolamine-selective phospholipase D (NAPE-PLD) and its degradation by fatty acid amide hydrolase (FAAH) in mouse embryos and oviducts creates locally an appropriate "anandamide tone" required for normal embryo development, oviductal transport, implantation, and pregnancy (see the related article beginning on page 2122). Adverse effects of elevated levels of anandamide on these processes resulting from FAAH inactivation are mimicked by administration of (-)-Delta9-tetrahydrocannabinol (THC; the major psychoactive constituent of marijuana), due to enhanced signaling via CB1. These findings show that exogenous THC can swamp endogenous anandamide signaling systems, thereby affecting multiple physiological processes.
Schuel
Herbert
H
Division of Anatomy and Cell Biology, Department of Pathology and Anatomical Sciences, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York 14214, USA. schuel@acsu.buffalo.edu
D000581:Amidohydrolases / Q000172:deficiency*; D000818:Animals; D001095:Arachidonic Acids / Q000502:physiology*; D002186:Cannabinoids / Q000378:metabolism; D004195:Disease Models, Animal; D063388:Endocannabinoids; D005187:Fallopian Tubes / Q000502:physiology*; D005260:Female; D006801:Humans; D051379:Mice; D009474:Neurons / Q000502:physiology; D053284:Polyunsaturated Alkamides; D011247:Pregnancy; D011248:Pregnancy Complications / Q000201:enzymology*; D043882:Receptors, Cannabinoid / Q000502:physiology; D015398:Signal Transduction; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D000099252:Fatty Acid Amide Hydrolases; C078814:anandamide