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Participation of D1–4 dopamine receptors in the pro-cognitive effects of angiotensin IV and des-Phe6 angiotensin IV

✍ Scribed by Jan J. Braszko


Book ID
104065112
Publisher
Elsevier Science
Year
2010
Tongue
English
Weight
596 KB
Volume
34
Category
Article
ISSN
0149-7634

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✦ Synopsis


Angiotensin IV (Ang IV) and des-Phe(6)Ang IV are naturally occurring neuroactive peptides of the renin-angiotensin system (RAS) involved in memory processing. However, the relevant mechanisms are poorly understood. In this review it is proposed that the pro-cognitive effects of these peptides are, at least partly, mediated by dopamine (DA). Recent studies demonstrated that the improvement of several memory aspects; recall of appetitively and aversively motivated behaviors and learning of spatial tasks by Ang IV and des-Phe(6)Ang IV was abolished, or significantly diminished by behaviorally inactive per se doses of the D(1) and D(2) receptor blockers SCH 23390 (R-[+]-7-chloro-8-hydroxy-3 methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) and remoxipride, respectively. The D(3) receptor inhibition with nafadotride was almost ineffective but again, the D(4) receptor blockade by L745,870 hydrochloride (3-{[4-(4-chlorophenyl)piperazin-1-yl]methyl}-1H-pyrrolo[2,3-b]pyridine hydrochloride) diminished all, except for spatial memory, improving actions of the peptides. These results suggest that Ang IV and des-Phe(6)Ang IV enhance memory in a brain region-specific manner, dependent on local DA receptor subpopulations and the memory aspects controlled by them. The data reviewed here, demonstrating DA-Ang IV and des-Phe(6)Ang IV interactions in brain, strongly suggest probability of clinically relevant effects of concomitant use of antipsychotic and RAS affecting drugs.


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## Abstract The aromatic amino acids Tyr and Phe in angiotensin IV (Ang IV) were conformationally constrained by the use of β‐Me substituted analogs, or cyclic constrained analogs. None of these modifications was allowed for Tyr^1^, while only __e__‐β‐MePhe^6^ substitution resulted in an AngIV anal