PMID- 20028450
OWN - NLM
STAT- MEDLINE
DCOM- 20100315
LR  - 20220309
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Linking)
VI  - 112
IP  - 5
DP  - 2010 Mar
TI  - Involvement of the AT1 receptor subtype in the effects of angiotensin IV and 
      LVV-haemorphin 7 on hippocampal neurotransmitter levels and spatial working 
      memory.
PG  - 1223-34
LID - 10.1111/j.1471-4159.2009.06547.x [doi]
AB  - Intracerebroventricular (i.c.v.) administration of angiotensin IV (Ang IV) or 
      Leu-Val-Val-haemorphin 7 (LVV-H7) improves memory performance in normal rats and 
      reverses memory deficits in rat models for cognitive impairment. These memory 
      effects were believed to be mediated via the putative 'AT4 receptor'. However, 
      this binding site was identified as insulin-regulated aminopeptidase (IRAP). 
      Correspondingly, Ang IV and LVV-H7 were characterised as IRAP inhibitors. This 
      study investigates whether and how IRAP may be involved in the central effects of 
      Ang IV and LVV-H7. We determined the effects of i.c.v. administration of Ang IV 
      or LVV-H7 on hippocampal neurotransmitter levels using microdialysis in rats. We 
      observed that Ang IV modulates hippocampal acetylcholine levels, whereas LVV-H7 
      does not. This discrepancy was reflected in the observation that Ang IV binds 
      with micromolar affinity to the AT1 receptor whereas no binding affinity was 
      observed for LVV-H7. Correspondingly, we demonstrated that the AT1 receptor is 
      involved in the effects of Ang IV on hippocampal neurotransmitter levels and on 
      spatial working memory in a plus maze spontaneous alternation task. However, the 
      AT1 receptor was not involved in the spatial memory facilitating effect of 
      LVV-H7. Finally, we demonstrated that Ang IV did not diffuse to the hippocampus 
      following i.c.v. injection, suggesting an extrahippocampal site of action. We 
      propose that AT1 receptors are implicated in the neurochemical and cognitive 
      effects of Ang IV, whereas LVV-H7 may mediate its effects via IRAP.
FAU - De Bundel, Dimitri
AU  - De Bundel D
AD  - Research Group Experimental Pharmacology, Department of Pharmaceutical Chemistry, 
      Drug Analysis and Drug Information, Vrije Universiteit Brussel, Brussels, 
      Belgium.
FAU - Demaegdt, Heidi
AU  - Demaegdt H
FAU - Lahoutte, Tony
AU  - Lahoutte T
FAU - Caveliers, Vicky
AU  - Caveliers V
FAU - Kersemans, Ken
AU  - Kersemans K
FAU - Ceulemans, Ann-Gaelle
AU  - Ceulemans AG
FAU - Vauquelin, Georges
AU  - Vauquelin G
FAU - Clinckers, Ralph
AU  - Clinckers R
FAU - Vanderheyden, Patrick
AU  - Vanderheyden P
FAU - Michotte, Yvette
AU  - Michotte Y
FAU - Smolders, Ilse
AU  - Smolders I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091217
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Hemoglobins)
RN  - 0 (Iodine Isotopes)
RN  - 0 (Neurotransmitter Agents)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 11128-99-7 (Angiotensin II)
RN  - 23025-68-5 (angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-)
RN  - 75808-66-1 (LVV-hemorphin-7)
SB  - IM
MH  - Angiotensin II/administration & dosage/*analogs & derivatives/pharmacokinetics
MH  - Animals
MH  - Dose-Response Relationship, Drug
MH  - Hemoglobins/*administration & dosage
MH  - Hippocampus/diagnostic imaging/*drug effects/metabolism
MH  - Injections, Intraventricular/methods
MH  - Iodine Isotopes/pharmacokinetics
MH  - Male
MH  - Maze Learning/drug effects
MH  - Memory, Short-Term/*drug effects
MH  - Microdialysis/methods
MH  - Neurotransmitter Agents/*metabolism
MH  - Peptide Fragments/*administration & dosage
MH  - Protein Binding/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Angiotensin, Type 1/*physiology
MH  - Space Perception/drug effects
MH  - Tissue Distribution/drug effects
MH  - Tomography, Emission-Computed, Single-Photon/methods
EDAT- 2009/12/24 06:00
MHDA- 2010/03/17 06:00
CRDT- 2009/12/24 06:00
PHST- 2009/12/24 06:00 [entrez]
PHST- 2009/12/24 06:00 [pubmed]
PHST- 2010/03/17 06:00 [medline]
AID - JNC6547 [pii]
AID - 10.1111/j.1471-4159.2009.06547.x [doi]
PST - ppublish
SO  - J Neurochem. 2010 Mar;112(5):1223-34. doi: 10.1111/j.1471-4159.2009.06547.x. Epub 
      2009 Dec 17.