PMID- 22729983
OWN - NLM
STAT- MEDLINE
DCOM- 20121120
LR  - 20211021
IS  - 1573-6903 (Electronic)
IS  - 0364-3190 (Linking)
VI  - 37
IP  - 9
DP  - 2012 Sep
TI  - Different interactions of prolyl oligopeptidase and neurotensin in dopaminergic 
      function of the rat nigrostriatal and mesolimbic pathways.
PG  - 2033-41
LID - 10.1007/s11064-012-0825-y [doi]
AB  - Prolyl oligopeptidase (PREP) is an intracellular enzyme digesting small 
      proline-containing peptides. Since PREP resides the same brain areas as 
      neurotensin in the nigrostriatal and mesolimbic dopaminergic pathways, we were 
      interested to study if there is an intracellular interaction between them. A 
      colocalization of PREP with neurotensin and neurotensin receptor 1 (NTS1) in the 
      rat striatum, nucleus accumbens (NAcc), substantia nigra (SN) and ventral 
      tegmental area (VTA) was studied with immunofluorescence. From the same brain 
      areas, the levels of dopamine and its metabolites were measured 1 h after the 
      injection of saline, NTS1 ligands (JMV-449; 5 mug) or antagonist (SR142948; 5 mug) 
      to the rat striatum or NAcc. We also studied whether an intraperitoneal injection 
      of a PREP inhibitor (KYP-2047; 5 mg/kg) affects the levels of dopamine and its 
      metabolites alone or modifies the effects of the NTS1 ligands. PREP was highly 
      colocalized with neurotensin and NTS1 in the VTA, and with NTS1 in the SN. 
      Colocalization was moderate or low in other brain areas. When injected to the 
      striatum, JMV-449 had a tendency to increase dopamine (p = 0.052) and metabolite 
      levels in the striatum and SN, whereas SR142948 did not. After the injection to 
      the NAcc, JMV-449 but not SR142948, increased dopamine levels in the VTA and 
      dopamine metabolite levels in the NAcc and VTA. KYP-2047 decreased the dopamine 
      levels in the striatum, but increased dopamine metabolite levels in the NAcc and 
      VTA. Our results suggest a novel role for PREP in the modulation of dopaminergic 
      transmission, which may be different in nigrostriatal and mesolimbic pathways.
FAU - Peltonen, I
AU  - Peltonen I
AD  - Division of Pharmacology and Toxicology, Faculty of Pharmacy, University of 
      Helsinki, Viikinkaari 5E, P.O. Box 56, 00014 Helsinki, Finland. 
      iida.peltonen@helsinki.fi
FAU - Myohanen, T T
AU  - Myohanen TT
FAU - Mannisto, P T
AU  - Mannisto PT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120623
PL  - United States
TA  - Neurochem Res
JT  - Neurochemical research
JID - 7613461
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Oligopeptides)
RN  - 0 (Pyrazoles)
RN  - 0 (Quinolines)
RN  - 0 (Receptors, Neurotensin)
RN  - 0 (SR 142948)
RN  - 0 (neurotensin type 1 receptor)
RN  - 139026-66-7 (JMV 449)
RN  - 39379-15-2 (Neurotensin)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.4.21.26 (Prolyl Oligopeptidases)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Chromatography, High Pressure Liquid
MH  - Corpus Striatum/drug effects/metabolism/*physiology
MH  - Dopamine/metabolism/*physiology
MH  - Enzyme Inhibitors/pharmacology
MH  - Injections, Intraventricular
MH  - Limbic System/drug effects/metabolism/*physiology
MH  - Male
MH  - Microscopy, Confocal
MH  - Microscopy, Fluorescence
MH  - Neural Pathways/drug effects/metabolism/*physiology
MH  - Neurotensin/*metabolism
MH  - Oligopeptides/pharmacology
MH  - Prolyl Oligopeptidases
MH  - Pyrazoles/pharmacology
MH  - Quinolines/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Neurotensin/drug effects/metabolism
MH  - Serine Endopeptidases/*metabolism
MH  - Stereotaxic Techniques
MH  - Substantia Nigra/drug effects/metabolism/*physiology
MH  - Ventral Tegmental Area/drug effects/metabolism
EDAT- 2012/06/26 06:00
MHDA- 2012/12/10 06:00
CRDT- 2012/06/26 06:00
PHST- 2012/04/10 00:00 [received]
PHST- 2012/06/08 00:00 [accepted]
PHST- 2012/06/05 00:00 [revised]
PHST- 2012/06/26 06:00 [entrez]
PHST- 2012/06/26 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
AID - 10.1007/s11064-012-0825-y [doi]
PST - ppublish
SO  - Neurochem Res. 2012 Sep;37(9):2033-41. doi: 10.1007/s11064-012-0825-y. Epub 2012 
      Jun 23.