Inhibition of NMDA receptor-mediated currents in isolated rat hippocampal neurones by adenosine A1 receptor activation.
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.
de Mendonça
A
A
Laboratory of Pharmacology, Gulbenkian Institute of Science, Hospital de Santa Maria, Lisboa, Portugal.
Sebastião
A M
AM
Ribeiro
J A
JA
D015762:2-Chloroadenosine / Q000494:pharmacology*; D000241:Adenosine / Q000031:analogs & derivatives*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D018047:Receptors, Purinergic P1 / Q000187:drug effects*
D016194:Receptors, N-Methyl-D-Aspartate; D018047:Receptors, Purinergic P1; D015762:2-Chloroadenosine; D000241:Adenosine