α2-Adrenoceptor-mediated inhibition of histamine release from rat cerebral cortical slices

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Abstract
1 Depolarization of rat cerebral cortical slices, prelabelled with [3H]-histidine, in high potassium (40 mM KCl) medium stimulated the release of [3H]-histamine. The K+-evoked release of [3H]-histamine was attenuated by incubation in calcium-free medium and prevented by prior incubation of brain slices with the selective histidine decarboxylase inhibitor S-(α)-fluoromethylhistidine. 2 The K+-evoked release of [3H]-histamine was significantly (P < 0.001) reduced following stimulation of histamine H3-receptors with R-(α)-methylhistamine (1 μm) and this effect was antagonized by the H3-antagonist thioperamide (1 μm). 3 Noradrenaline and the α2-selective adrenoceptor agonists clonidine and UK-14,304 inhibited the K+-evoked release of [3H]-histamine in a concentration-dependent manner yielding EC50 values of 2.5, 0.8 and 1.2 μm, respectively. However, the maximum response to clonidine was only 52 ± 8% of that obtained with noradrenaline. 4 The inhibitory effect of noradrenaline was antagonized by the non-selective α-antagonist phentolamine and by the selective α2-antagonists yohimbine and idazoxan. However, the response to noradrenaline was not inhibited by the α1-antagonist prazosin at concentrations up to 1 μm. 5 These results suggest that both histamine H 3-receptors and α2-adrenoceptors are present on histamine-containing nerve terminals in rat cerebral cortex and can exert an inhibitory influence on neurotransmitter release.
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