Participation of D 1-4 dopamine receptors in the pro-cognitive effects of angiotensin IV and des-Phe 6 angiotensin IV.
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.
Braszko
Jan J
JJ
Department of Clinical Pharmacology, Medical University of Bialystok, Waszyngtona 15 A, 15274 Bialystok, Poland. braszko@umwb.edu.pl
D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D018697:Nootropic Agents / Q000494:pharmacology*; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism; D050638:Receptors, Dopamine D4 / Q000378:metabolism
D018697:Nootropic Agents; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C496150:angiotensin IV, des-Phe(6)-; D000804:Angiotensin II; D050638:Receptors, Dopamine D4; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-