Inhibition by adenosine A(2A) receptors of NMDA but not AMPA currents in rat neostriatal neurons

Kerstin Wirkner, Heike Assmann, L. Köles, Zoltan Gerevich, Heike Franke, Wolfgang Nörenberg, Rudolf Boehm, Peter Illes

Research output: Article

69 Citations (Scopus)

Abstract

1. Whole-cell patch clamp experiments were used to investigate the transduction mechanism of adenosine A(2A) receptors in modulating N-methyl-D-aspartate (NMDA)-induced currents in rat striatal brain slices. The A(2A) receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680) inhibited the NMDA, but not the (S)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) current in a subset of striatal neurons. 2. Lucifer yellow-filled pipettes in combination with immunostaining of A(2A) receptors were used to identify CGS 21680-sensitive cells as typical medium spiny striatal neurons. 3. Dibutyryl cyclic AMP and the protein kinase A activator Sp-cyclic AMPs, but not the protein kinase A inhibitors Rp-cyclic AMPS or PKI(14-24)amide abolished the inhibitory effect of CGS 21680. The phospholipase C inhibitor U-73122, but not the inactive structural analogue U-73343 also interfered with CGS 21680. The activation of protein kinase C by phorbol 12-myristate 13-acetate or the blockade of this enzyme by staurosporine did not alter the effect of CGS 21680. Heparin, an antagonist of inositol 1,4,5-trisphosphate (InsP 3) and a more efficient buffering of intracellular Ca 2+ by BAPTA instead of EGTA in the pipette solution, abolished the CGS 21680-induced inhibition. 4. The calmodulin antagonist W-7 and cytochalasin B which enhances actin depolymerization also prevented the effect of CGS 21680; the calmodulin kinase II inhibitors CaM kinase II(281-309) and KN-93 but not the inactive structural analogue KN-92 were also effective. The calcineurin inhibitor deltamethrin did not interfere with CGS 21680. 5. It is suggested that the transduction mechanism of A(2A) receptors to inhibit NMDA receptor channels is the phospholipase C/InsP 3/calmodulin and calmodulin kinase II pathway. The adenylate cyclase/protein kinase A and phospholipase C/protein kinase C pathways do not appear to be involved.

Original languageEnglish
Pages (from-to)259-269
Number of pages11
JournalBritish Journal of Pharmacology
Volume130
Issue number2
Publication statusPublished - 2000

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Adenosine A2A Receptors
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
N-Methylaspartate
Neurons
Corpus Striatum
Type C Phospholipases
Cyclic AMP-Dependent Protein Kinases
Protein Kinase C
Calcium-Calmodulin-Dependent Protein Kinases
Calmodulin
Heparin Antagonists
Adenylate Kinase
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Bucladesine
Cytochalasin B
Inositol 1,4,5-Trisphosphate
Staurosporine
2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine
Egtazic Acid
Protein Kinase Inhibitors

ASJC Scopus subject areas

  • Pharmacology

Cite this

Wirkner, K., Assmann, H., Köles, L., Gerevich, Z., Franke, H., Nörenberg, W., ... Illes, P. (2000). Inhibition by adenosine A(2A) receptors of NMDA but not AMPA currents in rat neostriatal neurons. British Journal of Pharmacology, 130(2), 259-269.

Inhibition by adenosine A(2A) receptors of NMDA but not AMPA currents in rat neostriatal neurons. / Wirkner, Kerstin; Assmann, Heike; Köles, L.; Gerevich, Zoltan; Franke, Heike; Nörenberg, Wolfgang; Boehm, Rudolf; Illes, Peter.

In: British Journal of Pharmacology, Vol. 130, No. 2, 2000, p. 259-269.

Research output: Article

Wirkner, K, Assmann, H, Köles, L, Gerevich, Z, Franke, H, Nörenberg, W, Boehm, R & Illes, P 2000, 'Inhibition by adenosine A(2A) receptors of NMDA but not AMPA currents in rat neostriatal neurons', British Journal of Pharmacology, vol. 130, no. 2, pp. 259-269.
Wirkner, Kerstin ; Assmann, Heike ; Köles, L. ; Gerevich, Zoltan ; Franke, Heike ; Nörenberg, Wolfgang ; Boehm, Rudolf ; Illes, Peter. / Inhibition by adenosine A(2A) receptors of NMDA but not AMPA currents in rat neostriatal neurons. In: British Journal of Pharmacology. 2000 ; Vol. 130, No. 2. pp. 259-269.
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AU - Nörenberg, Wolfgang

AU - Boehm, Rudolf

AU - Illes, Peter

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