Modulation of N-methyl-D-aspartate (NMDA)-stimulated noradrenaline release in rat brain cortex by presynaptic alpha 2-adrenoceptors.

Rat brain cortex slices and synaptosomes preincubated with [3H]noradrenaline were used to investigate whether the NMDA-evoked noradrenaline release is modulated by agonists or antagonists at presynaptic alpha 2-adrenoceptors. In experiments on slices, noradrenaline and the preferential alpha-adrenoceptor agonists talipexole (former B-HT 920) and clonidine inhibited the NMDA-evoked tritium overflow whereas the selective alpha 1-adrenoceptor agonists cirazoline and methoxamine were ineffective. The alpha 2-adrenoceptor antagonists rauwolscine and idazoxan facilitated the NMDA-evoked tritium overflow whereas the preferential alpha 1-adrenoceptor antagonist prazosin was ineffective. The concentration-response curve of talipexole for its inhibitory effect on NMDA-evoked overflow was shifted to the right by idazoxan (apparent pA2 = 7.5). The EC50 of NMDA (97 mumol/l) for its stimulating effect on tritium overflow was not substantially changed by blockade of alpha 2-autoreceptors with 1 mumol/l rauwolscine (EC50 of NMDA in the presence of the alpha 2-adrenoceptor antagonist, 155 mumol/l), but the maximal overflow of tritium was increased 2.5 fold by this rauwolscine concentration. In experiments on synaptosomes, talipexole and noradrenaline inhibited the NMDA-evoked tritium overflow. The inhibitory effect of talipexole was abolished by idazoxan which, given alone, was ineffective, as was prazosin. Talipexole did also not produce an inhibition when tritium overflow was evoked by NMDA in the presence of omega-conotoxin GVIA 0.1 mumol/l; the latter, by itself, decreased the response to NMDA by about 55%.(ABSTRACT TRUNCATED AT 250 WORDS)