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Presynaptic Receptors for Dopamine, Histamine, and Serotonin

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Pharmacology of Neurotransmitter Release

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 184))

Presynaptic receptors for dopamine, histamine and serotonin that are located on dopaminergic, histaminergic and sertonergic axon terminals, respectively, function as autoreceptors. Presynaptic receptors also occur as heteroreceptors on other axon terminals. Auto- and heteroreceptors mainly affect Ca2+ -dependent exocytosis from the receptor-bearing nerve ending. Some additionally subserve other presynaptic functions.

Presynaptic dopamine, histamine and serotonin receptors are involved in various (patho)physiological conditions. Examples are the following:

Dopamine autoreceptors play a role in Parkinson’s disease, schizophrenia and drug addiction. Dopamine heteroreceptors affecting the release of acetylcholine and of amino acid neurotransmitters in the basal ganglia are also relevant for Parkinson’s disease. Peripheral dopamine heteroreceptors on postganglionic sympathetic terminals influence heart rate and vascular resistance through modulation of noradrenaline release.

Blockade of histamine autoreceptors increases histamine synthesis and release and may support higher CNS functions such as arousal, cognition and learning. Peripheral histamine heteroreceptors on C fiber and on postganglionic sympathetic fiber terminals diminish neuropeptide and noradrenaline release, respectively. Both inhibititory effects are beneficial in myocardial ischemia. The inhibition of neuropeptide release also explains the antimigraine effects of some agonists of presynaptic histamine receptors.

Upregulation of presynaptic serotonin autoreceptors is probably involved in the pathogenesis of major depression. Correspondingly, antidepressant treatments can be linked with a reduced density of 5-HT autoreceptors. 5-HT Heteroreceptor activation diminishes acetylcholine and GABA release and may therefore increase anxiety. In the periphery, presynaptic 5-HT heteroreceptor agonists shorten migraine attacks by inhibition of the release of neuropeptides from trigeminal afferents, apart from their constrictive action on meningeal vessels.

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Feuerstein, T.J. (2008). Presynaptic Receptors for Dopamine, Histamine, and Serotonin. In: Südhof, T.C., Starke, K. (eds) Pharmacology of Neurotransmitter Release. Handbook of Experimental Pharmacology, vol 184. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-74805-2_10

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