(TKP2021-EGA-23) Támogató: Innovációs és Technológiai Minisztérium
(TKP2021-EGA-25)
(OTKA-K128875)
(NKFI K 146086)
Szakterületek:
Gyógyszerészet, farmakogenomika, gyógyszerkutatás és tervezés, gyógyszeres kezelés
NMDA receptors in the prefrontal cortex (PFC) play a crucial role in cognitive functions.
Previous research has indicated that angiotensin II (Ang II) affects learning and
memory. This study aimed to examine how Ang II impacts NMDA receptor activity in layer
V pyramidal cells of the rat PFC. Whole-cell patch-clamp experiments were performed
in pyramidal cells in brain slices of 9–12-day-old rats. NMDA (30 μM) induced inward
currents. Ang II (0.001–1 µM) significantly enhanced NMDA currents in about 40% of
pyramidal cells. This enhancement was reversed by the AT1 antagonist eprosartan (1
µM), but not by the AT2 receptor antagonist PD 123319 (5 μM). When pyramidal neurons
were synaptically isolated, the increase in NMDA currents due to Ang II was eliminated.
Additionally, the dopamine D1 receptor antagonist SCH 23390 (10 μM) reversed the Ang
II-induced enhancement, whereas the D2 receptor antagonist sulpiride (20 μM) had no
effect. The potentiation of NMDA currents in a subpopulation of layer V pyramidal
neurons by Ang II, involving AT1 receptor activation and dopaminergic signaling, may
serve as an underlying mechanism for the effects of the renin–angiotensin system (RAS)
elements on neuronal functions.
