Presynaptic Receptors for Dopamine, Histamine, and Serotonin

Abstract

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 Ca(2+) -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.

Selective modulation of GABAergic tonic current by dopamine in the nucleus accumbens of alcohol-dependent rats

“…Changes in extracellular [GABA] may result from changes in the amount of released GABA or its uptake. Presynaptic effects of DA on neuronal GABA release are well-established (Feuerstein 2008;Zhang and Sulzer 2012), and we did observe decreases in frequency of mIPSCs after DA (30 nM) or quinpirole application, without concomitant changes in postsynaptic mIPSC kinetic parameters. These data suggested that the observed DA actions on I tonic might be mediated by changes in synaptic GABA release.…”

Serotonin and Blood Pressure Regulation

“…Neurotransmitter release is regulated locally by feedback inhibition through autoreceptors (adrenergic receptors that inhibit further NE release), and feedback inhibition of NE release can occur as a result of other chemicals, including 5-HT. Feuerstein (2008) published a comprehensive review of presynaptic receptors for dopamine, histamine, and 5-HT. Although autoinhibition of serotonergic nerves through 5-HT receptors makes intuitive sense, the finding of 5-HT receptors on adrenergic nerves is less intuitive.…”

Inhibition of Inflammatory Pain by Activating B-Type Natriuretic Peptide Signal Pathway in Nociceptive Sensory Neurons

“…Although autoreceptor-mediated regulatory mechanisms for classical neurotransmitters, such as dopamine and serotonin, are known to contribute to a local feedback mechanism in neural circuits (Feuerstein, 2008), evidence for autoreceptors in peptidergic system is still limited (Hökfelt et al, 2000). The presence of both BNP and NPR-A in peptidergic small DRG neurons and the effect of BNP on the firing rate of small DRG neurons suggest that NPR-A serves as an autoreceptor on some nociceptive afferent neurons.…”