KAINATE RECEPTORS ARE INVOLVED IN THE GLUTAMATE-INDUCED INDIRECT, PURINERGIC INHIBITION OF [H-3] NORADRENALINE RELEASE IN RABBIT BRAIN CORTEX

Activation of ionotropic but not of metabotropic glutamate receptors c auses an indirect inhibition of the release of noradrenaline in slices of rabbit brain cortex. The inhibition is mediated by adenosine which activates presynaptic adenosine A(1)-receptors. The present study cha racterizes the ionotropic receptor types through which glutamate itsel f produces this indirect inhibition. Rabbit brain cortex slices were p reincubated with [H-3]-noradrenaline, superfused with medium containin g desipramine (1 mu M) and stimulated electrically by trains of 6 puls es at 100 Hz. Glutamate (100-3000 mu M) reduced the electrically evoke d overflow of tritium by up to 58%. The effect did not differ 20 min a nd 60 min after addition of glutamate. Adenosine deaminase (1 U ml(-1) ) as well as 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 30 mu M) and D-gamma-glutamylamino-methanesulfonate (GAMS; 30 mu M), both of which block kainate receptors, attenuated the glutamate-induced inhibition. The NMDA receptor antagonist 2-amino-5-phosphonopentanoate (AP5; 100 m u M) and the AMPA receptor antagonist 6-nitro-7-sulfamoylbenzo(f)quino xaline-2,3-dione (NBQX; 30 mu M) did not change the effect of glutamat e. Given alone, CNQX and GAMS, but not AP5 and NBQX, slightly increase d the evoked overflow of tritium; the increases were abolished in the presence of adenosine deaminase. The results indicate that activation of kainate but not NMDA and AMPA receptors is involved in the indirect , adenosine-mediated inhibition by exogenous glutamate of the release of noradrenaline in rabbit brain cortex slices. Moreover, as shown by the increase caused by CNQX and GAMS, endogenous excitatory amino acid s inhibit the release of noradrenaline through the kainate receptor-ad enosine mechanism and thus contribute to the purinergic inhibitory con trol of noradrenaline release in the brain.