Morphine promotes rapid, arrestin-dependent endocytosis of mu-opioid receptors in striatal neurons. Export

@article{citeulike:384459, abstract = {Morphine activates mu-opioid receptors (MORs) without promoting their rapid endocytosis in a number of cell types. A previous study suggested that morphine can drive rapid redistribution of MORs in the nucleus accumbens, but it was not possible in this in vivo study to identify a specific membrane trafficking pathway affected by morphine, to exclude possible indirect actions of morphine via opiate-regulated neural circuitry, or to define the mechanism of this morphine-dependent regulation. In the present study, we addressed these questions using dissociated primary cultures of rat striatal neurons as a model system. Morphine promoted a rapid redistribution of both endogenous and recombinant MORs within 30 min after drug addition to the culture medium. This effect was mediated by rapid endocytosis and occurred in a cell-autonomous manner, as indicated by its detection in cells plated at low density and in cultures in which depolarization was blocked by tetrodotoxin. Morphine-induced endocytosis of MORs was quantitatively similar to that induced by the enkephalin analog D-Ala2-N-Me-Phe4-Glycol5-enkephalin, and endocytosis induced by both ligands was inhibited by a dominant-negative mutant version of arrestin-3 (beta-arrestin-2). These results extend previous in vivo results and indicate that morphine is indeed capable of driving rapid endocytosis of mu-opioid receptors in an important subset of opiate-responsive CNS neurons. They also suggest a cellular mechanism by which beta-arrestins may modulate the physiological effects of morphine in vivo.}, address = {Department of Psychiatry, University of California, San Francisco, California 94143, USA.}, author = {Haberstock-Debic, H. and Kim, K. A. and Yu, Y. J. and von Zastrow, M.}, citeulike-article-id = {384459}, citeulike-linkout-0 = {http://dx.doi.org/10.1523/JNEUROSCI.5045-04.2005}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16120787}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16120787}, day = {24}, doi = {10.1523/JNEUROSCI.5045-04.2005}, issn = {1529-2401}, journal = {J Neurosci}, keywords = {arrestin, endocytosis, opioid}, month = {August}, number = {34}, pages = {7847--7857}, posted-at = {2009-06-23 01:23:58}, priority = {3}, title = {Morphine promotes rapid, arrestin-dependent endocytosis of mu-opioid receptors in striatal neurons.}, url = {http://dx.doi.org/10.1523/JNEUROSCI.5045-04.2005}, volume = {25}, year = {2005} }

TY - JOUR ID - citeulike:384459 L3 - citeulike-article-id:384459 N2 - Morphine activates mu-opioid receptors (MORs) without promoting their rapid endocytosis in a number of cell types. A previous study suggested that morphine can drive rapid redistribution of MORs in the nucleus accumbens, but it was not possible in this in vivo study to identify a specific membrane trafficking pathway affected by morphine, to exclude possible indirect actions of morphine via opiate-regulated neural circuitry, or to define the mechanism of this morphine-dependent regulation. In the present study, we addressed these questions using dissociated primary cultures of rat striatal neurons as a model system. Morphine promoted a rapid redistribution of both endogenous and recombinant MORs within 30 min after drug addition to the culture medium. This effect was mediated by rapid endocytosis and occurred in a cell-autonomous manner, as indicated by its detection in cells plated at low density and in cultures in which depolarization was blocked by tetrodotoxin. Morphine-induced endocytosis of MORs was quantitatively similar to that induced by the enkephalin analog D-Ala2-N-Me-Phe4-Glycol5-enkephalin, and endocytosis induced by both ligands was inhibited by a dominant-negative mutant version of arrestin-3 (beta-arrestin-2). These results extend previous in vivo results and indicate that morphine is indeed capable of driving rapid endocytosis of mu-opioid receptors in an important subset of opiate-responsive CNS neurons. They also suggest a cellular mechanism by which beta-arrestins may modulate the physiological effects of morphine in vivo. IS - 34 JF - J Neurosci SN - 1529-2401 AD - Department of Psychiatry, University of California, San Francisco, California 94143, USA. EP - 7857 TI - Morphine promotes rapid, arrestin-dependent endocytosis of mu-opioid receptors in striatal neurons. VL - 25 SP - 7847 KW - arrestin KW - endocytosis KW - opioid AU - Haberstock-Debic, H AU - Kim, KA AU - Yu, YJ AU - von Zastrow, M PY - 2005/08/24/ UR - http://dx.doi.org/10.1523/JNEUROSCI.5045-04.2005 ER -