DARPP-32 mediates the actions of multiple drugs of abuse.

@article{citeulike:1378979, abstract = {Drugs of abuse share the ability to enhance dopaminergic neurotransmission in the dorsal and ventral striatum. The action of dopamine is modulated by additional neurotransmitters, including glutamate, serotonin and adenosine. All these neurotransmitters regulate the phosphorylation state of Dopamine- and cAMP-regulated phosphoprotein, Mr 32 kDa (DARPP-32). Phosphorylation at Thr(34) by protein kinase A converts DARPP-32 into a potent inhibitor of the multifunctional serine/threonine protein phosphatase, PP-1. Phosphorylation at Thr(75) by Cdk5 converts DARPP-32 into an inhibitor of protein kinase A. The state of phosphorylation of DARPP-32 at Thr(34) also depends on the phosphorylation state of Ser(97) and Ser(130), which are phosphorylated by CK2 and CK1, respectively. By virtue of regulation of these 4 phosphorylation sites, and through its ability to modulate the activity of PP-1 and protein kinase A, DARPP-32 plays a key role in integrating a variety of biochemical, electrophysiological, and behavioral responses controlled by dopamine and other neurotransmitters. Importantly, there is now a large body of evidence that supports a key role for DARPP-32-dependent signaling in mediating the actions of multiple drugs of abuse including cocaine, amphetamine, nicotine, caffeine, LSD, PCP, ethanol and morphine.}, address = {Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021, USA.}, author = {Svenningsson, P. and Nairn, A. C. and Greengard, P. }, citeulike-article-id = {1378979}, doi = {http://dx.doi.org/10.1208/aapsj070235}, issn = {1550-7416}, journal = {AAPS J}, keywords = {adenosine, camp, darpp-32, dopamine, glutamate, nitric-oxide, opioids, phosphorylation, pka, serotonin, steroids}, number = {2}, posted-at = {2007-06-11 17:53:03}, priority = {0}, title = {DARPP-32 mediates the actions of multiple drugs of abuse.}, url = {http://dx.doi.org/10.1208/aapsj070235}, volume = {7}, year = {2005} }

TY - JOUR ID - citeulike:1378979 L3 - citeulike-article-id:1378979 TI - DARPP-32 mediates the actions of multiple drugs of abuse. JF - AAPS J VL - 7 IS - 2 AD - Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021, USA. SN - 1550-7416 N2 - Drugs of abuse share the ability to enhance dopaminergic neurotransmission in the dorsal and ventral striatum. The action of dopamine is modulated by additional neurotransmitters, including glutamate, serotonin and adenosine. All these neurotransmitters regulate the phosphorylation state of Dopamine- and cAMP-regulated phosphoprotein, Mr 32 kDa (DARPP-32). Phosphorylation at Thr(34) by protein kinase A converts DARPP-32 into a potent inhibitor of the multifunctional serine/threonine protein phosphatase, PP-1. Phosphorylation at Thr(75) by Cdk5 converts DARPP-32 into an inhibitor of protein kinase A. The state of phosphorylation of DARPP-32 at Thr(34) also depends on the phosphorylation state of Ser(97) and Ser(130), which are phosphorylated by CK2 and CK1, respectively. By virtue of regulation of these 4 phosphorylation sites, and through its ability to modulate the activity of PP-1 and protein kinase A, DARPP-32 plays a key role in integrating a variety of biochemical, electrophysiological, and behavioral responses controlled by dopamine and other neurotransmitters. Importantly, there is now a large body of evidence that supports a key role for DARPP-32-dependent signaling in mediating the actions of multiple drugs of abuse including cocaine, amphetamine, nicotine, caffeine, LSD, PCP, ethanol and morphine. KW - adenosine KW - camp KW - darpp-32 KW - dopamine KW - glutamate KW - nitric-oxide KW - opioids KW - phosphorylation KW - pka KW - serotonin KW - steroids AU - Svenningsson, P AU - Nairn, AC AU - Greengard, P PY - 2005/// UR - http://dx.doi.org/10.1208/aapsj070235 ER -