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-(alpha)-fluoromethylhistidine. 2. The K+-evoked release of [3H]-histamine was significantly (P less than 0.001) reduced following stimulation of histamine H3-receptors with R-(alpha)-methylhistamine (1 microM) and this effect was antagonized by the H3-antagonist thioperamide (1 microM). 3. Noradrenaline and the alpha 2-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 microM, 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 alpha-antagonist phentolamine and by the selective alpha 2-antagonists yohimbine and idazoxan. However, the response to noradrenaline was not inhibited by the alpha 1-antagonist prazosin at concentrations up to 1 microM. 5. These results suggest that both histamine H3-receptors and alpha 2-adrenoceptors are present on histamine-containing nerve terminals in rat cerebral cortex and can exert an inhibitory influence on neurotransmitter release.