Mutual interaction of histamine H₃-receptors and α₂-adrenoceptors on noradrenergic terminals in mouse and rat rain cortex

Summary

Brain cortex slices were preincubated with ³H-noradrenaline and superfused with physiological salt solution containing desipramine. We studied the inhibition of the electrically evoked tritium overflow caused by histamine in the presence of α-adrenoceptor ligands (mouse and rat brain cortex), and the inhibition caused by talipexole (the former B-HT 920) in the presence of H₃-receptor ligands (mouse brain cortex).

In mouse brain cortex slices, the inhibitory effect of histamine on the tritium overflow evoked by 36 pulses, 0.3 Hz was not changed by the α₁-adrenoceptor antagonist prazosin, but increased by the α₂-adrenoceptor antagonist rauwolscine. When the current strength or the duration of electrical pulses was reduced to compensate for the increase in evoked tritium overflow produced by rauwolscine, the latter still. enhanced the effect of histamine. The histamine-induced inhibition of tritium overflow evoked by 360 pulses, 3 Hz was not affected by the α₁-adrenoceptor agonist phenylephrine but attenuated by the α₂-adrenoceptor- agonist talipexole. Finally, the inhibition by histamine of the tritium overflow evoked by 3 pulses, 100 Hz was attenuated by talipexole but not affected by rauwolscine. Conversely,. the inhibitory effect of talipexole on tritium overflow elicited by 360 pulses, 3 Hz was slightly attenuated by the H₃-receptor agonist R-(−)-α-methylhistamine but not, affected by the H₃- receptor antagonist thioperamide. In rat brain cortex slices, histamine only tended to inhibit tritium overflow evoked by 360 pulses, 3 Hz, both in the absence of α-adrenoceptor antagonists and in the presence of prazosin. However, histamine markedly inhibited the evoked overflow in the presence of rauwolscine. Again, enhancement of the histamine-induced inhibition also occurred when the current strength or the duration of pulses was reduced in order to compensate for the increase in evoked tritium overflow produced by rauwolscine.

The results suggest that the α₂-autoreceptors and the H₃-heteroreceptors at the noradrenergic nerve endings in the brain of mouse and rat interact with each other. Activation of the α₂-autoreceptors decreases, whereas blockade of the activated (but not of the non-activated) α₂-autoreceptors increases, the inhibitory effect of histamine. Activation of the H3-heteroreceptors slightly decreases, whereas blockade of the H₃-receptors fails to affect, the inhibitory effect of talipexole.