Historical Background
Identification of phosphodiesterase 10A (PDE10A) was first reported in mice and humans at the same period from three laboratories (Soderling et al. 1999; Fujishige et al. 1999a; Loughney et al. 1999). Primary sequence of PDE10A possesses a catalytic domain (HD domain) conserved within the 3, 5′-cyclic nucleotide phosphodiesterase family. PDE10A shows substrate specificity for both cyclic AMP (cAMP) and cyclic GMP (cGMP), and hydrolyzes these molecules to 5′-AMP and 5′-GMP, respectively. PDE10A mRNA and protein are highly expressed in the brain, particularly, in the striatal medium spiny neurons (Fujishige et al. 1999b; Seeger et al. 2003). Genetic deletion of PDE10A gene in mice as well as PDE10A inhibition by papaverine, a first reported PDE10 inhibitor, showed altered behavioral responses to several schizophrenia models (Siuciak et al. 2006; Siuciak et al. 2008); therefore, therapeutic implications of PDE10A inhibitor for psychiatric...
This is a preview of subscription content, log in via an institution.
References
Charych EI, Jiang LX, Lo F, Sullivan K, Brandon NJ. Interplay of palmitoylation and phosphorylation in the trafficking and localization of phosphodiesterase 10A: implications for the treatment of schizophrenia. J Neurosci. 2010;30:9027–37.
Coskran TM, Morton D, Menniti FS, Adamowicz WO, Kleiman RJ, Ryan AM, Strick CA, Schmidt CJ, Stephenson DT. Immunohistochemical localization of phosphodiesterase 10A in multiple mammalian species. J Histochem Cytochem. 2006;54:1205–13.
Fujishige K, Kotera J, Michibata H, Yuasa K, Takebayashi S, Okumura K, Omori K. Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both cAMP and cGMP (PDE10A). J Biol Chem. 1999a;274:18438–45.
Fujishige K, Kotera J, Omori K. Striatum- and testis-specific phosphodiesterase PDE10A isolation and characterization of a rat PDE10A. Eur J Biochem. 1999b;266:1118–27.
Grauer SM, Pulito VL, Navarra RL, Kelly MP, Kelley C, Graf R, Langen B, Logue S, Brennan J, Jiang L, Charych E, Egerland U, Liu F, Marquis KL, Malamas M, Hage T, Comery TA, Brandon NJ. Phosphodiesterase 10A inhibitor activity in preclinical models of the positive, cognitive, and negative symptoms of schizophrenia. J Pharmacol Exp Ther. 2009;331:574–90.
Gross-Langenhoff M, Hofbauer K, Weber J, Schultz A, Schultz JE. cAMP is a ligand for the tandem GAF domain of human phosphodiesterase 10 and cGMP for the tandem GAF domain of phosphodiesterase 11. J Biol Chem. 2006;281:2841–6.
Handa N, Mizohata E, Kishishita S, Toyama M, Morita S, Uchikubo-Kamo T, Akasaka R, Omori K, Kotera J, Terada T, Shirouzu M, Yokoyama S. Crystal structure of the GAF-B domain from human phosphodiesterase 10A complexed with its ligand, cAMP. J Biol Chem. 2008;283:19657–64.
Kehler J, Kilburn JP. Patented PDE10A inhibitors: novel compounds since 2007. Expert Opin Ther Pat. 2009;19:1715–25.
Kotera J, Fujishige K, Yuasa K, Omori K. Characterization and phosphorylation of PDE10A2, a novel alternative splice variant of human phosphodiesterase that hydrolyzes cAMP and cGMP. Biochem Biophys Res Commun. 1999;261:551–7.
Kotera J, Sasaki T, Kobayashi T, Fujishige K, Yamashita Y, Omori K. Subcellular localization of cyclic nucleotide phosphodiesterase type 10A variants, and alteration of the localization by cAMP-dependent protein kinase-dependent phosphorylation. J Biol Chem. 2004;279:4366–75.
Loughney K, Snyder PB, Uher L, Rosman GJ, Ferguson K, Florio VA. Isolation and characterization of PDE10A, a novel human 3′, 5′-cyclic nucleotide phosphodiesterase. Gene. 1999;234:109–17.
Matthiesen K, Nielsen J. Binding of cyclic nucleotides to phosphodiesterase 10A and 11A GAF domains does not stimulate catalytic activity. Biochem J. 2009;423:401–9.
Nishi A, Kuroiwa M, Miller DB, O’Callaghan JP, Bateup HS, Shuto T, Sotogaku N, Fukuda T, Heintz N, Greengard P, Snyder GL. Distinct roles of PDE4 and PDE10A in the regulation of cAMP/PKA signaling in the striatum. J Neurosci. 2008;28:10460–71.
Sano H, Nagai Y, Miyakawa T, Shigemoto R, Yokoi M. Increased social interaction in mice deficient of the striatal medium spiny neuron-specific phosphodiesterase 10A2. J Neurochem. 2008;105:546–56.
Schmidt CJ, Chapin DS, Cianfrogna J, Corman ML, Hajos M, Harms JF, Hoffman WE, Lebel LA, McCarthy SA, Nelson FR, Proulx-LaFrance C, Majchrzak MJ, Ramirez AD, Schmidt K, Seymour PA, Siuciak JA, Tingley 3rd FD, Williams RD, Verhoest PR, Menniti FS. Preclinical characterization of selective phosphodiesterase 10A inhibitors: a new therapeutic approach to the treatment of schizophrenia. J Pharmacol Exp Ther. 2008;325:681–90.
Seeger TF, Bartlett B, Coskran TM, Culp JS, James LC, Krull DL, Lanfear J, Ryan AM, Schmidt CJ, Strick CA, Varghese AH, Williams RD, Wylie PG, Menniti FS. Immunohistochemical localization of PDE10A in the rat brain. Brain Res. 2003;985:113–26.
Siuciak JA, Chapin DS, Harms JF, Lebel LA, McCarthy SA, Chambers L, Shrikhande A, Wong S, Menniti FS, Schmidt CJ. Inhibition of the striatum-enriched phosphodiesterase PDE10A: a novel approach to the treatment of psychosis. Neuropharmacology. 2006;51:386–96.
Siuciak JA, McCarthy SA, Chapin DS, Martin AN, Harms JF, Schmidt CJ. Behavioral characterization of mice deficient in the phosphodiesterase-10A (PDE10A) enzyme on a C57/Bl6N congenic background. Neuropharmacology. 2008;54:417–27.
Soderling SH, Bayuga SJ, Beavo JA. Isolation and characterization of a dual-substrate phosphodiesterase gene family: PDE10A. Proc Natl Acad Sci USA. 1999;96:7071–6.
Threlfell S, Sammut S, Menniti FS, Schmidt CJ, West AR. Inhibition of phosphodiesterase 10A increases the responsiveness of striatal projection neurons to cortical stimulation. J Pharmacol Exp Ther. 2009;328:785–95.
Xie Z, Adamowicz WO, Eldred WD, Jakowski AB, Kleiman RJ, Morton DG, Stephenson DT, Strick CA, Williams RD, Menniti FS. Cellular and subcellular localization of PDE10A, a striatum-enriched phosphodiesterase. Neuroscience. 2006;139:597–607.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this entry
Cite this entry
Sasaki, T., Kotera, J., Omori, K. (2012). Phosphodiesterase 10A. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0461-4_253
Download citation
DOI: https://doi.org/10.1007/978-1-4419-0461-4_253
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4419-0460-7
Online ISBN: 978-1-4419-0461-4
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences