Moving bliss: a new anandamide transporter

A study now identifies a protein that mediates the cellular transport of the lipophilic endocannabinoid anandamide in aqueous environments.

Similar to naming a newborn baby, scientists have to struggle with coming up with the appropriate designation for a newly identified entity that will suit it well for posterity. If the item is a newly identified molecule, one option is to simply name it by its chemical definition. If the scientists who discovered the first endogenous ligand for cannabinoid receptors in 1992 had chosen this option (1), we would have come to know the first endocannabinoid simply as N-arachidonoylethanolamide. In addition to being first-class chemists, however, the discoverers of the first endocannabinoid (1) were also very familiar with the history of science. They knew that the plant Cannabis sativa (marijuana) was regarded in India as early as 4,000 years ago as a sacred plant; thus, they named their discovery anandamide from the sanskrit word ananda, meaning "bliss, pure happiness, interior joy." Indeed, together with the identification of other elements of what we now call the endocannabinoid system, that discovery was real 'bliss' for generations of biologists fascinated by the plethora of different functions that this system exerts in the brain and in the body. In the present issue of Nature Neuroscience, Fu et al. (2) describe the molecular identity of the specific anandamide transporter that they named FLAT, and add another piece to our understanding of endocannabinoid signaling (2).

Anandamide is a lipid derivative of arachidonic acid that binds and activates G proteincoupled cannabinoid receptors (1). Anandamide, however, can also interact with several other targets at the plasma membrane (such as with some members of the transient potential receptor family and other ion channels) and in the intracellular space (nuclear peroxisome proliferator-activated receptors, PPARs) (3-5). In the brain, the best-characterized function of endocannabinoids is their ability to act as retrograde neurotransmitters. Under certain conditions, they are released by postsynaptic neurons (possibly also by other cells) and travel across the synaptic cleft to activate presynaptic type-1 cannabinoid receptors. Once at the presynaptic site, they are thought to decrease the liberation of classical neurotransmitters, such as glutamate or GABA, thus fine-tuning synaptic transmission (6). The action of endocannabinoids is terminated by cellular uptake and intracellular degradation, with the latter action being mainly mediated in the case of anandamide by a specific enzyme, the membranebound fatty acid amide hydrolase (FAAH-1) (7). As lipids, endocannabinoids move in cellular membranes with ease. However, the manner in which anandamide transport in aqueous media, such as the extracellular space and cytoplasm, is achieved is still an unresolved question. Earlier studies, employing drugs that block the cellular...