title: Kainate receptors are involved in the glutamate-induced indirect, purinergic inhibition of [3H]-noradrenaline release in rabbit brain cortex.
abstract: Activation of ionotropic but not metabotropic glutamate receptors causes an indirect inhibition of the release of noradrenaline in slices of rabbit brain cortex. The inhibition is mediated by adenosine which activates presynaptic adenosine A1-receptors. The present study characterizes the ionotropic receptor types through which glutamate itself produces this indirect inhibition. Rabbit brain cortex slices were preincubated with [3H]-noradrenaline, superfused with medium containing desipramine (1 microM) and stimulated electrically by trains of 6 pulses at 100 Hz. Glutamate (100-3000 micro M) reduced the electrically evoked overflow of tritium by up to 58%. The effect did not differ 20 min and 60 min after addition of glutamate. Adenosine deaminase (1 U ml-1) as well as 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 30 microM) and D-gamma-glutamylamino-methanesulfonate (GAMS; 30 micro M), both of which block kainate receptors, attenuated the glutamate-induced inhibition. The NMDA receptor antagonist 2-amino-5-phosphonopentanoate (AP5; 100 micro M) and the AMPA receptor antagonist 6-nitro-7-sulfamoylbenzo(f)-quinoxaline-2,3-dione (NBQX; 30 micro M) did not change the effect of glutamate. Given alone, CNQX and GAMS, but not AP5 and NBQX, slightly increased 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 acids inhibit the release of noradrenaline through the kainate receptor-adenosine mechanism and thus contribute to the purinergic inhibitory control of noradrenaline release in the brain.
authors: Pharmakologisches Institut, Universität Freiburg, Germany.
authors: I
authors: I
authors: von Kugelgen
authors: K
authors: K
authors: Starke
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000241:Adenosine / Q000502:physiology*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D005260:Female; D018698:Glutamic Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011817:Rabbits; D017470:Receptors, Glutamate / Q000502:physiology; D018092:Kainic Acid Receptors / Q000502:physiology*; D014970:Xanthines / Q000494:pharmacology
chemical_list: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000241:Adenosine; D018698:Glutamic Acid; D009638:Norepinephrine; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine