Pre-synaptic control by histamine H3 receptors of neurotransmitter release

Abstract

Histamine regulates pre- and post-synaptically several brain functions, through the interaction with G protein-coupled receptors. Four such receptors (H1-H4) have been cloned, and three of them (H1, H2, and H3) are widely distributed in the mammalian nervous system. The histamine H3 receptor (H3R) was first identified in 1983 by Arrang and colleagues as an auto-receptor controlling histamine synthesis and release. Although H3Rs can be found in the periphery, mainly on axons of sympathetic and parasympathetic neurons, the central nervous system contains the great majority of such receptors, and the comparison with mRNA levels indicates that in most areas H3Rs are expressed on nerve terminals. Several lines of evidence have shown that in addition to its function as auto-receptor, the H3R regulates as a hetero-receptor the release of a number of neuroactive substances, namely acetylcholine, 5-hydroxytryptamine (5-HT, serotonin), noradrenaline, dopamine, glutamate, γ-aminobutyric acid (GABA) and substance P. In this work we review the reported actions of H3R activation on neurotransmitter release. © Springer Science+Business Media B.V. 2010.