Alpha 2-adrenoceptor-mediated inhibition of histamine release from rat cerebral cortical slices.
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.
Hill
S J
SJ
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham.
Straw
R M
RM
D000818:Animals; D000068438:Brimonidine Tartrate; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*
D018377:Neurotransmitter Agents; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D000068438:Brimonidine Tartrate; D003000:Clonidine; D011188:Potassium; D009638:Norepinephrine