DARPP-32 mediates the actions of multiple drugs of abuse
Journal Title: The AAPS Journal - Year 2005, Vol 7, Issue 2
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 Dopaminal serine/threonine protein phosphatase, PP-1. Phosphorylatine- and cAMP-regulated phosphoprotein, Mr 32 kDa (DARPP-32). Phosphorylation at Thr34 by protein kinase A converts DARPP-32 into a potent inhibitor of the multifunctioon at Thr75 by Cdk5 converts DARPP-32 into an inhibitor of protein kinase A. The state of phosphorylation of DARPP-32 at Thr34 also depends on the phosphorylation state of Ser97 and Ser130, 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 alarge 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.
Authors and Affiliations
Per Svenningsson, Angus C. Nairn, Paul Greengard
Keywords
Related Articles
- EP ID EP681858
- DOI 10.1208/aapsj070235
- Views 89
- Downloads 0
Reversed phase-high performance liquid chromatographic method to measure migration of semivolatile compound, vanillin, in ipratropium bromide inhalation solution
Pharmacokinetic Interaction between the Flavonoid Luteolin and γ-Hydroxybutyrate in Rats: Potential Involvement of Monocarboxylate Transporters
Monocarboxylate transporter 1 (MCT1) has been previously reported as an important determinant of the renal reabsorption of the drug of abuse, γ-hydroxybutyrate (GHB). Luteolin is a potent MCT1 inhibitor, inhibiti...
The Pharmacokinetics and Interactions of Ivermectin in Humans—A Mini-review
Ivermectin is an antiparasitic drug with a broad spectrum of activity, high efficacy as well as a wide margin of safety. Since 1987, this compound has a widespread use in veterinary medicine and it use has been extended...
Simulation of Monoclonal Antibody Pharmacokinetics in HumansUsing a Minimal Physiologically Based Model
The online version of this article (doi:10.1208/s12248-014-9640-5) contains supplementary material, which is available to authorized users.
Light-scattering investigations on dilute nonionic oil-in-water microemulsions
Dilute 3-component nonionic oil-in-water microemulsions formulated with either a polyoxyethylene surfactant (C18∶1E10 or C12E10) or the alkylamine-N-oxide surfactant, DDAO (C12AO), and containing either a triglyc...