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α 2 ‐Adrenoceptor‐mediated inhibition of histamine release from rat cerebral cortical slices
Author(s) -
Hill S.J.,
Straw R.M.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11758.x
Subject(s) - histamine , yohimbine , thioperamide , prazosin , phentolamine , histamine h3 receptor , endocrinology , medicine , idazoxan , chemistry , antagonist , histidine decarboxylase , stimulation , receptor , biology , biochemistry , amino acid , histidine
1 Depolarization of rat cerebral cortical slices, prelabelled with [ 3 H]‐histidine, in high potassium (40 mM KCl) medium stimulated the release of [ 3 H]‐histamine. The K + ‐evoked release of [ 3 H]‐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 [ 3 H]‐histamine was significantly (P < 0.001) reduced following stimulation of histamine H 3 ‐receptors with R‐(α)‐methylhistamine (1 μ m ) and this effect was antagonized by the H 3 ‐antagonist thioperamide (1 μ m ). 3 Noradrenaline and the α 2 ‐selective adrenoceptor agonists clonidine and UK‐14,304 inhibited the K + ‐evoked release of [ 3 H]‐histamine in a concentration‐dependent manner yielding EC 50 values of 2.5, 0.8 and 1.2 μ m , 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 α 2 ‐antagonists yohimbine and idazoxan. However, the response to noradrenaline was not inhibited by the α 1 ‐antagonist prazosin at concentrations up to 1 μ m . 5 These results suggest that both histamine H 3 ‐receptors and α 2 ‐adrenoceptors are present on histamine‐containing nerve terminals in rat cerebral cortex and can exert an inhibitory influence on neurotransmitter release.