Dopamine D-2 and Adenosine A(2A) Receptors Interaction on Ca2+ Current Modulation in a Rodent Model of Parkinsonism
Por:
Rendon-Ochoa, Ernesto Alberto, Padilla-Orozco, Montserrat, Calderon, Vladimir Melesio, Aviles-Rosas, Victor Hugo, Hernandez-Gonzalez, Omar, Hernandez-Flores, Teresa, Perez-Ramirez, Maria Belen, Palomero-Rivero, Marcela, Galarraga, Elvira, BARGAS, JOSE
Publicada:
1 jun 2022
Resumen:
Adenosine A(1) and A(2A) receptors are expressed in striatal projection
neurons (SPNs). A(1) receptors are located in direct (dSPN) and indirect
SPNs (iSNP). A(2A) receptors are only present in iSPNs. Dopamine D-2
receptors are also expressed in iSPNs and interactions between D-2 and
A(2A) receptors have received attention. iSPNs activity increases during
parkinsonism (PD) and A(2A) receptors may be responsible by enhancing
Ca2+ currents (iCa(2+)). Therefore, A(2A) receptors blockade is a
therapeutic approach. We asked whether A(2A) receptors need the
interaction with D-2 receptors (D2R) to exert their actions. By using
isolated and identified iSPNs to avoid indirect influences, we show that
D2R action habilitates A(2A) receptors (A(2A)R) modulation. iCa(2+)
through voltage gated Ca2+ channels (Ca-V) was used as a signal to
observe this interaction. Voltage-clamp recordings in acutely
dissociated iSPNs, current-clamp recordings in slices and calcium
imaging in transgenic A(2A)-Cre mice, showed that D2R reduction in
iCa(2+) endows A(2A)R to restore iCa(2+) on iSPNs showing an
antagonistic interaction between D-2 and A(2A) receptors. A(2A)
receptors were blocked by the antagonist istradefylline, however, this
blockade differed in control and dopamine-depleted iSPNs: istradefylline
reduced D2R modulation in parkinsonian animals as compared to controls.
Calcium imaging recordings show that istradefylline occludes D2R actions
in the parkinsonian circuitry and this effect depends on the order of
drugs application. Thus, while D-2 activation enables A(2A) receptors
action, blockade of A(2A)R induces a reduction in the action of D-2
agonists, confirming a complex interaction. Summary Statement A(2A)
receptor required previous D-2 receptor activation to modulate Ca2+
currents. Istradefylline decreases pramipexole modulation on Ca2+
currents. Istradefylline reduces A(2A) + neurons activity in striatial
microcircuit, but pramipexole failed to further reduce neuronal
activity.
Filiaciones:
Rendon-Ochoa, Ernesto Alberto:
Univ Nacl Autonoma Mexico, Fac Estudios Super Iztacala, Unidad Invest Interdisciplinaria & Ciencias Salud, Lab Psicofarmacol, Tlalnepantla, Mexico
Padilla-Orozco, Montserrat:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Div Neurociencias, Ciudad De Mexico, Mexico
Calderon, Vladimir Melesio:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Div Neurociencias, Ciudad De Mexico, Mexico
Aviles-Rosas, Victor Hugo:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Div Neurociencias, Ciudad De Mexico, Mexico
Hernandez-Gonzalez, Omar:
Univ Nacl Autonoma Mexico, Fac Med, Dept Fisiol, Circuito Exterior S-N Ciudad Univ, Ciudad De Mexico, Mexico
Hernandez-Flores, Teresa:
Okinawa Inst Sci & Technol, Brain Mech Behav Unit, Onna, Okinawa, Japan
Perez-Ramirez, Maria Belen:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Div Neurociencias, Ciudad De Mexico, Mexico
Palomero-Rivero, Marcela:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Div Neurociencias, Ciudad De Mexico, Mexico
Galarraga, Elvira:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Div Neurociencias, Ciudad De Mexico, Mexico
BARGAS, JOSE:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Div Neurociencias, Ciudad De Mexico, Mexico
gold, Green Published, All Open Access, Gold, Green
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