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Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor

Abstract

Although histaminergic neurones have not yet been histochemically visualized, there is little doubt that histamine (HA) has a neurotransmitter role in the invertebrate and mammalian central nervous system1,2. For example, a combination of biochemical, electrophysiological and lesion studies in rats have shown that histamine is synthesized in and released from a discrete set of neurones ascending through the lateral hypothalamic area and widely projecting in the telencephalon3–5. Histamine acts on target cells in mammalian brain via stimulation of two classes of receptor (H1 and H2) previously characterized in peripheral organs6,7 and probably uses Ca2+ and cyclic AMP, respectively, as second messengers8–10. It is well established that several neurotransmitters affect neuronal activity in the central nervous system through stimulation not only of postsynaptic receptors, but also of receptors located presynaptically which often display distinct pharmacological specificity and by which they may control their own release. Such ‘autoreceptors’ have been demonstrated (or postulated) in the case of noradrenaline, dopamine, serotonin, acetylcholine and γ-aminobutyric acid (GABA) neurones11,12 but have never been demonstrated for histamine. We show here that histamine inhibits its own release from depolarized slices of rat cerebral cortex, an action apparently mediated by a class of receptor (H3) pharmacologically distinct from those previously characterized, that is, the H1 and H2 receptors.

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Arrang, JM., Garbarg, M. & Schwartz, JC. Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor. Nature 302, 832–837 (1983). https://doi.org/10.1038/302832a0

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