Effects of α-adrenoceptor antagonists on the release of serotonin and noradrenaline from rat brain cortex slices

Summary

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.

In conclusion, when neuronal uptake was inhibited, all α-adrenoceptor antagonists investigated increased, i.e. disinhibited, the evoked³H overflow from slices labelled with³H-noradrenaline, whereas there were differences between the compounds, when neuronal noradrenaline uptake was operative; these differences were not related to their imidazoline, phenylethylamine or indolealkylamine structure or their own ability to inhibit the neuronal uptake of noradrenaline. The apparent pA₂ values of the α-adrenoceptor antagonists were independent of the chemical structure of the agonists against which these values were determined (derivatives of imidazoline or phenylethylamine). The α-adrenoceptor on the serotoninergic nerve terminals of the cortex slices do not appear to be activated by endogenous noradrenaline released from neighbouring noradrenergic fibres.