Inhibition of NMDA receptor-mediated currents in isolated rat hippocampal neurones by adenosine A1 receptor activation

Neuroreport. 1995 May 30;6(8):1097-100. doi: 10.1097/00001756-199505300-00006.

Abstract

The effect of the stable adenosine analogue, 2-chloro-adenosine (CADO), on the currents elicited by iontophoretic application of N-methyl-D-aspartate (NMDA) to pyramidal cells acutely dissociated from the CA1 area of the rat hippocampus was studied using the patch-clamp technique in the whole-cell configuration. CADO (3-300 nM) reversibly inhibited NMDA receptor-mediated currents (maximal effect: 54.2 +/- 6.6% decrease, EC50 = 10.3 nM). This effect was prevented by the adenosine A1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (50 nM). CADO (100 nM inhibited the conductance induced by iontophoretic application of NMDA, without changing its reversal potential, in both the absence and the presence of Mg2+ (30 microM). Adenosine may contribute to the regulation of the NMDA receptor function, particularly under conditions, like hypoxia and ischaemia, leading to excessive NMDA receptor activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Chloroadenosine / pharmacology*
  • Adenosine / analogs & derivatives*
  • Animals
  • Dose-Response Relationship, Drug
  • Hippocampus / drug effects*
  • Membrane Potentials / drug effects
  • Patch-Clamp Techniques
  • Pyramidal Cells / drug effects
  • Rats
  • Rats, Inbred Strains
  • Receptors, N-Methyl-D-Aspartate / drug effects*
  • Receptors, Purinergic P1 / drug effects*

Substances

  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Purinergic P1
  • 2-Chloroadenosine
  • Adenosine