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

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

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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 (InsP3) and a more efficient buffering of intracellular Ca2+ 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/InsP3/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
DOIs
Publication statusPublished - Jan 1 2000

Keywords

  • AMPA receptor
  • Adenosine A(2A) receptor
  • NMDA receptor
  • Patch clamp
  • Striatum

ASJC Scopus subject areas

  • Pharmacology

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    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, 130(2), 259-269. https://doi.org/10.1038/sj.bjp.0703234