Internalization and Recycling of the CB1 Cannabinoid Receptor

@article{citeulike:3056654, abstract = {Abstract : Tolerance develops rapidly to cannabis, cannabinoids, and related drugs acting at the CB1 cannabinoid receptor. However, little is known about what happens to the receptor as tolerance is developing. In this study, we have found that CB1 receptors are rapidly internalized following agonist binding and receptor activation. Efficacious cannabinoid agonists (WIN 55,212-2, CP 55,940, and HU 210) caused rapid internalization. Methanandamide (an analogue of an endogenous cannabinoid, anandamide) was less effective, causing internalization only at high concentration, whereas 03949-tetrahydrocannabinol caused little internalization, even at 3 03BCM. CB1 internalized via clathrin-coated pits as sequestration was inhibited by hypertonic sucrose. Internalization did not require activated G protein 03B1i, 03B1o, or 03B1s subunits. A region of the extreme carboxy terminus of the receptor was necessary for internalization, as a mutant CB1 receptor lacking the last 14 residues did not internalize, whereas a mutant lacking the last 10 residues did. Steps involved in the recycling of sequestered receptor were also investigated. Recovery of CB1 to the cell surface after short (20 min) but not long (90 min) agonist treatment was independent of new protein synthesis. Recycling also required endosomal acidification and dephosphorylation. These results show that CB1 receptor trafficking is dynamically regulated by cannabimimetic drugs.}, address = {Departments of Physiology and Biophysics and of Anesthesiology, University of Washington School of Medicine, Seattle, Washington, U.S.A.}, author = {Hsieh, C. and Brown, S. and Derleth, C. and Mackie, K.}, citeulike-article-id = {3056654}, doi = {10.1046/j.1471-4159.1999.0730493.x}, journal = {Journal of Neurochemistry}, keywords = {recycling}, number = {2}, pages = {493--501}, posted-at = {2008-07-29 13:25:45}, priority = {2}, title = {Internalization and Recycling of the CB1 Cannabinoid Receptor}, url = {http://dx.doi.org/10.1046/j.1471-4159.1999.0730493.x}, volume = {73}, year = {1999} }

TY - JOUR ID - citeulike:3056654 L3 - citeulike-article-id:3056654 N2 - Abstract : Tolerance develops rapidly to cannabis, cannabinoids, and related drugs acting at the CB1 cannabinoid receptor. However, little is known about what happens to the receptor as tolerance is developing. In this study, we have found that CB1 receptors are rapidly internalized following agonist binding and receptor activation. Efficacious cannabinoid agonists (WIN 55,212-2, CP 55,940, and HU 210) caused rapid internalization. Methanandamide (an analogue of an endogenous cannabinoid, anandamide) was less effective, causing internalization only at high concentration, whereas 03949-tetrahydrocannabinol caused little internalization, even at 3 03BCM. CB1 internalized via clathrin-coated pits as sequestration was inhibited by hypertonic sucrose. Internalization did not require activated G protein 03B1i, 03B1o, or 03B1s subunits. A region of the extreme carboxy terminus of the receptor was necessary for internalization, as a mutant CB1 receptor lacking the last 14 residues did not internalize, whereas a mutant lacking the last 10 residues did. Steps involved in the recycling of sequestered receptor were also investigated. Recovery of CB1 to the cell surface after short (20 min) but not long (90 min) agonist treatment was independent of new protein synthesis. Recycling also required endosomal acidification and dephosphorylation. These results show that CB1 receptor trafficking is dynamically regulated by cannabimimetic drugs. IS - 2 JF - Journal of Neurochemistry AD - Departments of Physiology and Biophysics and of Anesthesiology, University of Washington School of Medicine, Seattle, Washington, U.S.A. EP - 501 TI - Internalization and Recycling of the CB1 Cannabinoid Receptor VL - 73 SP - 493 KW - recycling AU - Hsieh, C AU - Brown, S AU - Derleth, C AU - Mackie, K PY - 1999/// UR - http://dx.doi.org/10.1046/j.1471-4159.1999.0730493.x ER -