title: The novel nonapeptide acein targets angiotensin converting enzyme in the brain and induces dopamine release.
abstract: OBJECTIVE
  Using an in-house bioinformatics programme, we identified and synthesized a novel nonapeptide, H-Pro-Pro-Thr-Thr-Thr-Lys-Phe-Ala-Ala-OH. Here, we have studied its biological activity, in vitro and in vivo, and have identified its target in the brain.
  
  
  METHODS
  The affinity of the peptide was characterized using purified whole brain and striatal membranes from guinea pigs and rats . Its effect on behaviour in rats following intra-striatal injection of the peptide was investigated. A photoaffinity UV cross-linking approach combined with subsequent affinity purification of the ligand covalently bound to its receptor allowed identification of its target.
  
  
  RESULTS
  The peptide bound with high affinity to a single class of binding sites, specifically localized in the striatum and substantia nigra of brains from guinea pigs and rats. When injected within the striatum of rats, the peptide stimulated in vitro and in vivo dopamine release and induced dopamine-like motor effects. We purified the target of the peptide, a ~151 kDa protein that was identified by MS/MS as angiotensin converting enzyme (ACE I). Therefore, we decided to name the peptide acein.
  
  
  CONCLUSIONS
  The synthetic nonapeptide acein interacted with high affinity with brain membrane-bound ACE. This interaction occurs at a different site from the active site involved in the well-known peptidase activity, without modifying the peptidase activity. Acein, in vitro and in vivo, significantly increased stimulated release of dopamine from the brain. These results suggest a more important role for brain ACE than initially suspected.
authors.affiliation: Faculté de Pharmacie, Institut des Biomolécules Max Mousseron (IBMM) UMR 5247, Université de Montpellier, CNRS, ENSCM, Montpellier, France.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Neasta
authors.affiliation: Faculté de Pharmacie, Institut des Biomolécules Max Mousseron (IBMM) UMR 5247, Université de Montpellier, CNRS, ENSCM, Montpellier, France.
authors.forename: Charlène
authors.initials: C
authors.lastname: Valmalle
authors.affiliation: INSERM UMR 952, Physiopathologie des Maladies du Système Nerveux Central, Paris, France.
authors.forename: Anne-Claire
authors.initials: AC
authors.lastname: Coyne
authors.affiliation: Faculté de Pharmacie, Institut des Biomolécules Max Mousseron (IBMM) UMR 5247, Université de Montpellier, CNRS, ENSCM, Montpellier, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Carnazzi
authors.affiliation: Faculté de Pharmacie, Institut des Biomolécules Max Mousseron (IBMM) UMR 5247, Université de Montpellier, CNRS, ENSCM, Montpellier, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Subra
authors.affiliation: Faculté de Pharmacie, Institut des Biomolécules Max Mousseron (IBMM) UMR 5247, Université de Montpellier, CNRS, ENSCM, Montpellier, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Galleyrand
authors.affiliation: Faculté de Pharmacie, Institut des Biomolécules Max Mousseron (IBMM) UMR 5247, Université de Montpellier, CNRS, ENSCM, Montpellier, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Gagne
authors.affiliation: Faculté de Pharmacie, Institut des Biomolécules Max Mousseron (IBMM) UMR 5247, Université de Montpellier, CNRS, ENSCM, Montpellier, France.
authors.forename: Céline
authors.initials: C
authors.lastname: M'Kadmi
authors.affiliation: Faculté de Pharmacie, Institut des Biomolécules Max Mousseron (IBMM) UMR 5247, Université de Montpellier, CNRS, ENSCM, Montpellier, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bernad
authors.affiliation: Faculté de Pharmacie, Institut des Biomolécules Max Mousseron (IBMM) UMR 5247, Université de Montpellier, CNRS, ENSCM, Montpellier, France.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Bergé
authors.affiliation: Faculté de Pharmacie, Institut des Biomolécules Max Mousseron (IBMM) UMR 5247, Université de Montpellier, CNRS, ENSCM, Montpellier, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Cantel
authors.affiliation: Institut de Génomique Fonctionnelle, UMR5203, INSERM U661, Rue de la Cardonille, Université de Montpellier, Montpellier, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Marin
authors.affiliation: Faculté de Pharmacie, Institut des Biomolécules Max Mousseron (IBMM) UMR 5247, Université de Montpellier, CNRS, ENSCM, Montpellier, France.
authors.forename: Jacky
authors.initials: J
authors.lastname: Marie
authors.affiliation: Faculté de Pharmacie, Institut des Biomolécules Max Mousseron (IBMM) UMR 5247, Université de Montpellier, CNRS, ENSCM, Montpellier, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Banères
authors.affiliation: CIRB, Collège de France, 11, Place Marcelin Berthelot, Paris, France.
authors.forename: Marie-Lou
authors.initials: ML
authors.lastname: Kemel
authors.affiliation: INSERM UMR 952, Physiopathologie des Maladies du Système Nerveux Central, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Daugé
authors.affiliation: Faculté de Pharmacie, Institut des Biomolécules Max Mousseron (IBMM) UMR 5247, Université de Montpellier, CNRS, ENSCM, Montpellier, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Puget
authors.affiliation: Faculté de Pharmacie, Institut des Biomolécules Max Mousseron (IBMM) UMR 5247, Université de Montpellier, CNRS, ENSCM, Montpellier, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Martinez
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D020134:Catalytic Domain / Q000187:drug effects; D019295:Computational Biology; D004298:Dopamine / Q000378:metabolism*; D006168:Guinea Pigs; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009842:Oligopeptides; D007703:Peptidyl-Dipeptidase A; D004298:Dopamine