Angiotensin IV Receptors in the Rat Prefrontal Cortex: Neuronal Expression and NMDA Inhibition

被引:1
|
作者
Papp, Zsolt Tamas [1 ,2 ]
Ribiczey, Polett [1 ,2 ]
Kato, Erzsebet [2 ]
Toth, Zsuzsanna E. [3 ]
Varga, Zoltan V. [2 ]
Giricz, Zoltan [2 ]
Hanuska, Adrienn [1 ,2 ]
Al-Khrasani, Mahmoud [2 ]
Zsembery, Akos [1 ]
Zelles, Tibor [1 ,2 ,4 ]
Harsing Jr, Laszlo G. [2 ]
Koles, Laszlo [1 ,2 ]
机构
[1] Semmelweis Univ, Dept Oral Biol, H-1089 Budapest, Hungary
[2] Semmelweis Univ, Dept Pharmacol & Pharmacotherapy, H-1089 Budapest, Hungary
[3] Semmelweis Univ, Dept Anat Histol & Embryol, Lab Neuroendocrinol & Situ Hybridizat, H-1094 Budapest, Hungary
[4] HUN REN Inst Expt Med, Lab Mol Pharmacol, H-1083 Budapest, Hungary
关键词
N-methyl-D-aspartate receptor; AT(4) angiotensin receptor; insulin-regulated aminopeptidase; prefrontal cortex; renin-angiotensin system; neuromodulation; INSULIN-REGULATED AMINOPEPTIDASE; V PYRAMIDAL NEURONS; AT(4) RECEPTOR; BINDING-SITES; DOPAMINE-RECEPTORS; INTERNATIONAL UNION; SPATIAL MEMORY; BRAIN; POTENT; IDENTIFICATION;
D O I
10.3390/biomedicines13010071
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: N-methyl-D-aspartate type glutamate receptors (NMDARs) are fundamental to neuronal physiology and pathophysiology. The prefrontal cortex (PFC), a key region for cognitive function, is heavily implicated in neuropsychiatric disorders, positioning the modulation of its glutamatergic neurotransmission as a promising therapeutic target. Our recently published findings indicate that AT(1) receptor activation enhances NMDAR activity in layer V pyramidal neurons of the rat PFC. At the same time, it suggests that alternative angiotensin pathways, presumably involving AT(4) receptors (AT4Rs), might exert inhibitory effects. Angiotensin IV (Ang IV) and its analogs have demonstrated cognitive benefits in animal models of learning and memory deficits. Methods: Immunohistochemistry and whole-cell patch-clamp techniques were used to map the cell-type-specific localization of AT4R, identical to insulin-regulated aminopeptidase (IRAP), and to investigate the modulatory effects of Ang IV on NMDAR function in layer V pyramidal cells of the rat PFC. Results: AT4R/IRAP expression was detected in pyramidal cells and GABAergic interneurons, but not in microglia or astrocytes, in layer V of the PFC in 9-12-day-old and 6-month-old rats. NMDA (30 mu M) induced stable inward cation currents, significantly inhibited by Ang IV (1 nM-1 mu M) in a subset of pyramidal neurons. This inhibition was reproduced by the IRAP inhibitor LVVYP-H7 (10-100 nM). Synaptic isolation of pyramidal neurons did not affect the Ang IV-mediated inhibition of NMDA currents. Conclusions: Ang IV/IRAP-mediated inhibition of NMDA currents in layer V pyramidal neurons of the PFC may represent a way of regulating cognitive functions and thus a potential pharmacological target for cognitive impairments and related neuropsychiatric disorders.
引用
收藏
页数:19
相关论文
共 50 条
  • [41] Clozapine and haloperidol differentially modulate the basal rate and pattern of neuronal firing and the effects of NMDA antagonists in awake rat prefrontal cortex
    Homayoun, H
    Moghaddam, B
    SCHIZOPHRENIA BULLETIN, 2005, 31 (02) : 301 - 302
  • [42] ROLE OF NMDA AND NON-NMDA RECEPTORS IN SYNAPTIC TRANSMISSION IN RAT PIRIFORM CORTEX
    JUNG, MW
    LARSON, J
    LYNCH, G
    EXPERIMENTAL BRAIN RESEARCH, 1990, 82 (02) : 451 - 455
  • [43] Adrenergic modulation of NMDA receptors in prefrontal cortex is differentially regulated by RGS proteins and spinophilin
    Liu, Wenhua
    Yuen, Eunice Y.
    Allen, Patrick B.
    Feng, Jian
    Greengard, Paul
    Yan, Zhen
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (48) : 18338 - 18343
  • [44] Dynamic modulation of NMDA-induced responses by ifenprodil in rat prefrontal cortex
    Zhang, XX
    Shi, WX
    SYNAPSE, 2001, 39 (04) : 313 - 318
  • [45] Impaired Attention and Synaptic Senescence of the Prefrontal Cortex Involves Redox Regulation of NMDA Receptors
    Guidi, Michael
    Kumar, Ashok
    Foster, Thomas C.
    JOURNAL OF NEUROSCIENCE, 2015, 35 (09): : 3966 - 3977
  • [46] Glial D-serine gates NMDA receptors at excitatory synapses in prefrontal cortex
    Turpin, Fabrice R.
    Fossat, Pascal
    Sacchi, Silvia
    Dulong, Jerome
    Shi, Ting
    Rivet, Jean-Michel
    Sweedler, Jonathan V.
    Pollegioni, Loredano
    Millan, Mark J.
    Oliet, Stephane H. R.
    Mothet, Jean-Pierre
    AMINO ACIDS, 2011, 41 : S45 - S45
  • [47] Activation of NMDA receptors in the medial prefrontal cortex attenuates the cardiovascular response to acute stress
    Mueller-Ribeiro, Flavia Camargos
    Zaretsky, Dmitry V.
    Zaretskaia, Maria V.
    DiMicco, Joseph A.
    Fontes, Marco Peliky
    FASEB JOURNAL, 2011, 25
  • [48] Glial D-Serine Gates NMDA Receptors at Excitatory Synapses in Prefrontal Cortex
    Fossat, Pascal
    Turpin, Fabrice R.
    Sacchi, Silvia
    Dulong, Jerome
    Shi, Ting
    Rivet, Jean-Michel
    Sweedler, Jonathan V.
    Pollegioni, Loredano
    Millan, Mark J.
    Oliet, Stephane H. R.
    Mothet, Jean-Pierre
    CEREBRAL CORTEX, 2012, 22 (03) : 595 - 606
  • [49] The Contribution of AMPA and NMDA Receptors to Persistent Firing in the Dorsolateral Prefrontal Cortex in Working Memory
    van Vugt, Bram
    van Kerkoerle, Timo
    Vartak, Devavrat
    Roelfsema, Pieter R.
    JOURNAL OF NEUROSCIENCE, 2020, 40 (12): : 2458 - 2470
  • [50] Potentiation of NMDA receptor currents by dopamine D1 receptors in prefrontal cortex
    Chen, GJ
    Greengard, P
    Yan, Z
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (08) : 2596 - 2600