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Gene Review

Prep  -  prolyl endopeptidase

Rattus norvegicus

Synonyms: PE, Post-proline cleaving enzyme, Prolyl endopeptidase, rPop
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Disease relevance of Prep

  • JTP-4819 ((S)-2-[[(S)-2-(hydroxyacetyl)-1-pyrrolidinyl]carbonyl]-N- phenylmethyl)-1-pyrrolidinecarboxamide) is a potent (IC50: 0.83 +/- 0.09 nM in rat brain supernatant; 5.43 +/- 0.81 nM in Flavobacterium meningosepticum) and specific inhibitor of prolyl endopeptidase (PEP) [1].
  • Normalization of STZ induced hyperglycemia by sodium metavanadate treatment or by replacement of exogenous insulin did not restore pancreatic PE activity [2].
  • Compound S 17092 is a potent and selective inhibitor of prolyl endopeptidase (EC, PEP) that may be of therapeutic value for the treatment of memory impairment associated with neurodegenerative diseases [3].
  • We investigated the effects of the prolyl endopeptidase inhibitors 1-[1-(Benzyloxycarbonyl)-L-prolyl]prolinal (Z-Pro-Prolinal) and N-benzyloxycarbonyl-thioprolyl-thioprolinal-dimethylaceta l (ZTTA) on delayed neuronal death induced by four-vessel-occlusion transient ischemia in rats [4].
  • We investigated the effect of N-benzyloxycarbonyl-thioprolyl-thioprolinal-dimethylaceta l (ZTTA), a novel postproline cleaving enzyme (prolyl endopeptidase, PPCE) inhibitor, on the in vitro activity of rat brain PPCE and memory impairment induced by cerebral ischemia [5].

Psychiatry related information on Prep

  • In this report, the pharmacological actions of JTP-4819, a novel specific prolyl endopeptidase (PEP) inhibitor devised for the treatment of Alzheimer's disease, are reviewed with respect to its effects on PEP activity, neuropeptidergic and cholinergic neurons, and memory-related behavior in rats [6].
  • Protective effect of eurystatins A and B, new prolyl endopeptidase inhibitors, on scopolamine-induced amnesia in rats [7].

High impact information on Prep


Biological context of Prep


Anatomical context of Prep

  • Caudal epididymal spermatozoa from rats with CRF but not from controls had been filtrated via Sperm Prep tubes to isolate the sperm fraction showing strong forward progressions [16].
  • In this study, a 35% phosphoric acid gel (3M Scotchbond etchant), a nonrinse etchant (NRC), and two EDTA-containing conditioners (RC-Prep and File-Eze) were tested in vitro for blocking nerve conductance evoked in the rat sciatic nerve after local application [12].
  • The enhancement of PE activity following STZ treatment was specific for pancreas tissue [2].
  • In this work, we analyzed the effects of certain volume and/or osmotic changes in the activity of the soluble and membrane-bound prolyl endopeptidase in several brain areas, heart, lungs, kidney and adrenal and pituitary glands of the rat [17].
  • Pharmacological studies of a novel prolyl endopeptidase inhibitor, JTP-4819, in rats with middle cerebral artery occlusion [18].

Associations of Prep with chemical compounds

  • Prolyl endopeptidase (EC, PEP), a serine protease that hydrolyzes peptides at the carboxyl side of proline residues, is involved in the breakdown of several proline-containing neuropeptides and, thus, may contribute to the regulation of behavioral activities [19].
  • The aldehyde was found to be a remarkably potent inhibitor of prolyl endopeptidase with a Ki of 14 nM [11].
  • Their relative concentrations were ANG II >or= ANG-(1-7) > ANG III, and accumulation was modulated by quinapril, an inhibitor of angiotensin-converting enzyme (ACE), Z-proprolinal (ZPP), an inhibitor of prolyl endopeptidase (PEP), and parachloromercurylsulfonic acid (PCMS), an inhibitor of sulfhydryl protease [20].
  • Rat serum catalyzed the degradation of 67.5 nmoles substrate/ml serum/h. The data indicate that TRH is degraded in rat serum predominantly by "thyroliberinase" and that prolyl endopeptidase and pyroglutamyl peptide hydrolase do not contribute significantly to this process [21].
  • The identity of the enzymes catalyzing the degradation of thyrotropin releasing hormone (TRH) in rat serum was investigated by the use of specific inhibitors of prolyl endopeptidase and pyroglutamyl peptide hydrolase [21].

Other interactions of Prep


Analytical, diagnostic and therapeutic context of Prep


  1. JTP-4819: a novel prolyl endopeptidase inhibitor with potential as a cognitive enhancer. Toide, K., Iwamoto, Y., Fujiwara, T., Abe, H. J. Pharmacol. Exp. Ther. (1995) [Pubmed]
  2. Enhancement by streptozotocin-induced diabetes of pancreatic prolyl endopeptidase activity in neonatal rats. Salers, P. Regul. Pept. (1994) [Pubmed]
  3. Effect of prolyl endopeptidase inhibition on arginine-vasopressin and thyrotrophin-releasing hormone catabolism in the rat brain. Bellemère, G., Vaudry, H., Morain, P., Jégou, S. J. Neuroendocrinol. (2005) [Pubmed]
  4. Effects of prolyl endopeptidase inhibitors and neuropeptides on delayed neuronal death in rats. Shishido, Y., Furushiro, M., Tanabe, S., Shibata, S., Hashimoto, S., Yokokura, T. Eur. J. Pharmacol. (1999) [Pubmed]
  5. ZTTA, a postproline cleaving enzyme inhibitor, improves cerebral ischemia-induced deficits in a three-panel runway task in rats. Shishido, Y., Furushiro, M., Tanabe, S., Nishiyama, S., Hashimoto, S., Ohno, M., Yamamoto, T., Watanabe, S. Pharmacol. Biochem. Behav. (1996) [Pubmed]
  6. A novel prolyl endopeptidase inhibitor, JTP-4819--its behavioral and neurochemical properties for the treatment of Alzheimer's disease. Toide, K., Shinoda, M., Miyazaki, A. Reviews in the neurosciences. (1998) [Pubmed]
  7. Protective effect of eurystatins A and B, new prolyl endopeptidase inhibitors, on scopolamine-induced amnesia in rats. Kamei, H., Ueki, T., Obi, Y., Fukagawa, Y., Oki, T. Jpn. J. Pharmacol. (1992) [Pubmed]
  8. Effect of a novel prolyl endopeptidase inhibitor, JTP-4819, on prolyl endopeptidase activity and substance P- and arginine-vasopressin-like immunoreactivity in the brains of aged rats. Toide, K., Okamiya, K., Iwamoto, Y., Kato, T. J. Neurochem. (1995) [Pubmed]
  9. Delineation of a particulate thyrotropin-releasing hormone-degrading enzyme in rat brain by the use of specific inhibitors of prolyl endopeptidase and pyroglutamyl peptide hydrolase. Friedman, T.C., Wilk, S. J. Neurochem. (1986) [Pubmed]
  10. Peptide-degrading enzymatic activities in GH3 cells and rat anterior pituitary homogenates. Friedman, T.C., Orlowski, M., Wilk, S. Endocrinology (1984) [Pubmed]
  11. Inhibition of rabbit brain prolyl endopeptidase by n-benzyloxycarbonyl-prolyl-prolinal, a transition state aldehyde inhibitor. Wilk, S., Orlowski, M. J. Neurochem. (1983) [Pubmed]
  12. Effects of current and potential dental etchants on nerve compound action potentials. Cehreli, Z.C., Onur, M.A., Taşman, F., Gümrükçüoğlu, A., Artuner, H. Journal of endodontics. (2002) [Pubmed]
  13. Vascular response of current and potential dental etchants. Cehreli, Z.C., Onur, M.A., Taşman, F., Gümrükçuölu, A. Journal of endodontics. (2002) [Pubmed]
  14. Comparative study of kallikrein-like serine proteinases from rat submandibular glands. Bedi, G.S. Prep. Biochem. Biotechnol. (1996) [Pubmed]
  15. Changes in prolyl endopeptidase during maturation of rat brain and hydrolysis of substance P by the purified enzyme. Kato, T., Nakano, T., Kojima, K., Nagatsu, T., Sakakibara, S. J. Neurochem. (1980) [Pubmed]
  16. Effects of chronic renal failure on the sperm fertilizing capacity. Yamamoto, Y., Sofikitis, N., Miyagawa, I. Urologia internationalis. (1997) [Pubmed]
  17. Effects of hydrosaline treatments on prolyl endopeptidase activity in rat tissues. Irazusta, J., Silveira, P.F., Gil, J., Varona, A., Casis, L. Regul. Pept. (2001) [Pubmed]
  18. Pharmacological studies of a novel prolyl endopeptidase inhibitor, JTP-4819, in rats with middle cerebral artery occlusion. Shinoda, M., Matsuo, A., Toide, K. Eur. J. Pharmacol. (1996) [Pubmed]
  19. Localization of the mRNA encoding prolyl endopeptidase in the rat brain and pituitary. Bellemère, G., Vaudry, H., Mounien, L., Boutelet, I., Jégou, S. J. Comp. Neurol. (2004) [Pubmed]
  20. Localized accumulation of angiotensin II and production of angiotensin-(1-7) in rat luteal cells and effects on steroidogenesis. Pepperell, J.R., Nemeth, G., Yamada, Y., Naftolin, F., Merino, M. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  21. The effect of inhibitors of prolyl endopeptidase and pyroglutamyl peptide hydrolase on TRH degradation in rat serum. Friedman, T.C., Wilk, S. Biochem. Biophys. Res. Commun. (1985) [Pubmed]
  22. Degradation of ACTH/MSH(4-10) and its synthetic analog semax by rat serum enzymes: an inhibitor study. Potaman, V.N., Alfeeva, L.Y., Kamensky, A.A., Nezavibatko, V.N. Peptides (1993) [Pubmed]
  23. Proline-specific proteases in cultivated neuronal and glial cells. Mentlein, R., von Kolszynski, M., Sprang, R., Lucius, R. Brain Res. (1990) [Pubmed]
  24. ZTTA, a prolyl endopeptidase inhibitor, potentiates the arginine-vasopressin-induced incorporation of [14C]leucine in rat amygdaloid and cortical slices. Shishido, Y., Tanaka, T., Tanabe, S., Furushiro, M., Hashimoto, S., Yokokura, T., Shibata, S., Watanabe, S. Pharm. Res. (1999) [Pubmed]
  25. Effect of aging on rat tissue peptidase activities. Agirregoitia, N., Gil, J., Ruiz, F., Irazusta, J., Casis, L. J. Gerontol. A Biol. Sci. Med. Sci. (2003) [Pubmed]
  26. Morphine withdrawal alters anterior pituitary hormone secretion, brain endopeptidase activity and brain monoamine metabolism in the rat. Idänpään-Heikkilä, J.J., Rauhala, P., Tuominen, R.K., Tuomainen, P., Zolotov, N., Männistö, P.T. Pharmacol. Toxicol. (1996) [Pubmed]
  27. Cathepsin B and prolyl endopeptidase activity in rat peritoneal and alveolar macrophages. Stimulation of peritoneal macrophages by saline lavage. Lesser, M., Chang, J.C., Orlowski, J., Kilburn, K.H., Orlowski, M. J. Lab. Clin. Med. (1983) [Pubmed]
  28. Prolyl endopeptidase inhibitors. Hermecz, I., Kánai, K. Farmaco (2000) [Pubmed]
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