Effects of alpha-adrenoceptor antagonists on the release of serotonin and noradrenaline from rat brain cortex slices. Influence of noradrenaline uptake inhibition and determination of pA2 values.

Rat brain cortex slices preincubated with3H-noradrenaline or3H-serotonin were superfused with physiological salt solution. The effects of α-adrenoceptor antagonists (phentolamine, BDF 6143, BE 2254 and rauwolscine) on the electrically evoked3H overflow and their interactions with clonidine or noradrenaline were studied. The effects of these antagonists on tritium accumulation by slices incubated with either3H-monoamine were also examined. 1. In the absence of cocaine, the evoked tritium overflow from slices labelled with3H-noradrenaline was facilitated by rauwolscine and, more markedly, phentolamine, whereas BDF 6143 and BE 2254 were ineffective. In the presence of cocaine, the evoked3H overflow was increased by all α-adrenoceptor antagonists. At decreased temperature (17 instead of 37° C), BDF 6143 facilitated the evoked overflow. 2. In the absence or presence of cocaine, the evoked3H overflow from slices labelled with3H-serotonin was not affected by BDF 6143 or BE 2254 at concentrations up to 1 and 0.1 μmol/l, respectively. BDF 6143 10 μmol/l decreased the evoked3H overflow. 3. The concentration-response curve of clonidine or noradrenaline for their inhibitory effects on the evoked3H overflow from slices labelled with3H-serotonin were shifted to the right by BDF 6143 or BE 2254. The apparent pA2 values of BDF 6143 against clonidine or noradrenaline were 9.22 and 9.02, respectively, and the corresponding values of BE 2254 were 8.16 and 7.92, respectively. 4. Tritium accumulation by slices incubated with3H-noradrenaline or3H-serotonin was not affected by rauwolscine or BDF 6143, but it was inhibited by rather high concentrations of phentolamine or BE 2254 (IC50>1 μmol/l). Tritium accumulation by slices incubated with3H-noradrenaline was also decreased when the temperature was reduced from 37 to 17° C.