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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...
- 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.CrossRefPubMedGoogle Scholar
- 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.CrossRefPubMedGoogle Scholar
- 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.PubMedCrossRefGoogle Scholar