IONOTROPIC GLUTAMATE-RECEPTOR TYPES LEADING TO ADENOSINE-MEDIATED INHIBITION OF ELECTRICALLY-EVOKED [(3)H]-NORADRENALINE RELEASE IN RABBIT BRAIN CORTEX SLICES

1 Glutamate inhibits the electrically evoked release of noradrenaline in rabbit brain cortex slices; the inhibition is mediated by adenyl co mpounds, presumably adenosine. The aim of the present study was to ide ntify the receptors involved in this indirect inhibitory effect of glu tamate. Slices of the occipitoparietal cortex were preincubated with [ H-3]-noradrenaline and then superfused and stimulated by trains of 6 p ulses, 100 Hz. 2 The ionotropic glutamate receptor agonists lpha-amino -3-hydroxy-5-methylisoxazole4-propionate (AMPA; 10-100 muM), kainate ( 10-100 muM) and N-methyl-D-aspartate (NMDA; 30-300 muM) but not the me tabotropic glutamate receptor agonist, 1-amino-1,3-cyclopentanedicarbo xylate (ACPD; 10-100 muM) reduced the electrically evoked overflow of tritium. 3 The effects of AMPA, kainate and NMDA were attenuated or ab olished by the adenosine A1-receptor antagonist, 8-cyclopentyl-1,3-dip ropylxanthine (DPCPX) as well as by adenosine deaminase but not by the alpha2-adrenoceptor antagonist yohimbine, the gamma-aminobutyric acid (GABA) receptor antagonists, bicuculline and 2-hydroxysaclofen- and t he NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). 4 The NMDA receptor antagonist, 2-amino-5-phosphonopentanoate (AP5) bl ocked the inhibitory effect of NMDA but not that of AMPA and kainate. The non-NMDA-receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) blocked the effect of AMPA but not of kainate and NMDA. 5 In a ddition to decreasing the electrically evoked overflow of tritium, AMP A, kainate and NMDA but not ACPD caused a steep but transient rise of basal tritium efflux. This immediate releasing effect was not signific antly changed by DPCPX, adenosine deaminase, yohimbine, bicuculline, 2 -hydroxy-saclofen and L-NAME (except that L-NAME enhanced the effect o f kainate). AP5 and CNQX antagonized the immediate releasing effects i n the same way that they antagonized the inhibition by AMPA, kainate a nd NMDA of the electrically evoked overflow of tritium. 6 It is conclu ded that AMPA, kainate and NMDA, like glutamate, reduce the electrical ly evoked release of noradrenaline by releasing adenosine or an adenin e nucleotide which is then degraded to adenosine. Activation of each o f the three ionotropic glutamate receptors, AMPA, kainate and NMDA rec eptors, but not activation of metabotropic glutamate receptors can ini tiate this indirect inhibitory effect on the release of noradrenaline (as well as the known noradrenaline releasing effect).