Transport of endocannabinoids across the plasma membrane and within the cell

• Published in: The FEBS journal 2013-05, Vol.280 (9), p.1895-1904
• Main Author: Fowler, Christopher J.
• Format: Article
• Language: English
• Subjects: 2-arachidonoylglycerol; adiposomes; Amidohydrolases - antagonists & inhibitors; Amidohydrolases - physiology; anandamide; Animals; Arachidonic Acids - metabolism; Biological Transport; cannabinoid; carrier molecules; Cell adhesion & migration; Cell Membrane - metabolism; cellular uptake; Cholesterol - physiology; endocannabinoid; Endocannabinoids - metabolism; Enzyme Inhibitors - pharmacology; fatty acid amide hydrolase; fatty-acid-binding proteins; Humans; membrane translocation; Membrane Transport Proteins - physiology; Membranes; Plasma; Polyunsaturated Alkamides - metabolism; transport; transport/carrier molecules
• ISSN: 1742-464X; 1742-4658; 1742-4658
• DOI: 10.1111/febs.12212

Endocannabinoids are readily accumulated from the extracellular space by cells. Although their uptake properties have the appearance of a process of facilitated diffusion, it is by no means clear as to whether there is a plasma membrane transporter dedicated to this task. Intracellular carrier proteins that shuttle the endocannabinoid anandamide from the plasma membrane to its intracellular targets such as the metabolic enzyme, fatty acid amide hydrolase, have been identified. These include proteins with other primary functions, such as fatty‐acid‐binding proteins and heat shock protein 70, and possibly a fatty acid amide hydrolase‐like anandamide transporter protein. Thus, anandamide uptake can be adequately described as a diffusion process across the plasma membrane followed by intracellular carrier‐mediated transport to effector molecules, catabolic enzymes and sequestration sites, although it is recognized that different cells are likely to utilize different mechanisms of endocannabinoid transport depending upon the utility of the endocannabinoid for the cell in question. The mechanisms whereby the endocannabinoids anandamide and 2‐arachidonoylglycerol are accumulated in cells are reviewed. In the author's view, anandamide uptake can be adequately described as a diffusion process across the plasma membrane followed by intracellular carrier‐mediated transport to effector molecules, catabolic enzymes and sequestration sites, although different cells are likely to utilise different mechanisms of endocannabinoid transport.