Neuronal histamine, function

Histaminergic neurons can regulate and be regulated by other neurotransmitter systems. A number of other transmitter systems can interact with histaminergic neurons (Table 14-1). As mentioned, the H3 receptor is thought to function as an inhibitory heteroreceptor. Thus, activation of brain H3 receptors decreases the release of acetylcholine, dopamine, norepinephrine, serotonin and certain peptides. However, histamine may also increase the activity of some of these systems through H, and/or H2 receptors. Activation of NMDA, p opioid, dopamine D2 and some serotonin receptors can increase the release of neuronal histamine, whereas other transmitter receptors seem to decrease release. Different patterns of interactions may also be found in discrete brain regions. 

Histamine in the nervous system may participate in a variety of brain functions. Several of the suspected physiological roles for histamine are related to its ability to increase the neuronal excitability [1, 2,15]. For example, mutant mice lacking the H, receptor show defective locomotor and exploratory behaviors [57], Neuronal histamine may increase attention and/or arousal by many mechanisms, including by enhancing sensory input [58], All available evidence from several species shows that histaminergic neurons, when activated, increase wakefulness... 

In various brain areas neuronal histamine release and synthesis is regulated presynaptically by histamine H3 receptors [1]. Recent studies revestl that H3 receptors not only act as autoreceptors to regulate the release euid synthesis of histamine [2, 3], but also modulate the release of other neurotransmitters, like acetylcholine [4], serotonin [5], dopamine [6] and noradrenaline [7]. In view of these widespread modulatory activities of the histamine H3 receptors, important roles for this receptor subtype in the various mammalian brain functions have been indicated [8, 9]. Consequently, selective ligands for the H3 receptor have been suggested to be benificial in the treatment of e.g. epilepsia, Alzheimer disease, sleeping and attention-deficit disorders [10, 11,12, 13, 14, 15,16],... 

After an overview of neurotransmitter systems and function and a consideration of which substances can be classified as neurotransmitters, section A deals with their release, effects on neuronal excitability and receptor interaction. The synaptic physiology and pharmacology and possible brain function of each neurotransmitter is then covered in some detail (section B). Special attention is given to acetylcholine, glutamate, GABA, noradrenaline, dopamine, 5-hydroxytryptamine and the peptides but the purines, histamine, steroids and nitric oxide are not forgotten and there is a brief overview of appropriate basic pharmacology. 

It is important to emphasise that a lesion of the reticular system disrupts a number of afferent inputs to the cortex. Particularly important in this respect are the mono-aminergic (especially noradrenaline, 5-HT and histamine) and cholinergic pathways. When the ascending inputs from these neurons are destroyed, sleep is passive and not at all like natural sleep which, as detailed above, has distinct phases and depends on brainstem influences on cortical function. How these different neurotransmitters might influence sleep and arousal will be considered next. 

Although histamine is not stored in neurons outside of the central nervous system, mast-cell-derived histamine can modify peripheral sensory nerve function. Both acute and chronic pain states can result from inflammation or peripheral nerve cell injury, and there is substantial evidence that mast cell histamine participates in these disorders. 

Deficiency of this coenzyme can lead to many manifestations. Clinical signs include retarded growth, acrodynia, alopecia, skeletal changes and anemia, while changes in neurotransmitters, such as dopamine, serotonin, norepinephrine (noradrenaline), tryptamine, tyramine, histamine, y-aminobutyric acid, and taurine, affect the brain function and can lead to seizures and convulsions. An overdose of vitamin Bg leads to neuronal damage and sensory and motor effects [417],... 

The neurotransmitter histamine (HA) exerts several functions in the hypothalamus [1-2] including an involvement in the neuroendocrine regulation of pituitary hormone secretion [3]. HA has no effect directly at the level of the pituitary gland, but influences the secretion of anterior pituitary hormones either by an exerted e.g. in the paraventricular nucleus (PVN) on other central transmitters or hypothalamic regulating factors, which subsequently regulate the release of anterior pituitary hormones. In addition, HA acts on the supraoptic nucleus (SON) in the hypothalamus where the posterior pituitary hormones are synthesized and thereby exerts a direct effect on the release of the posterior pituitary hormones. Immunohistochemical studies have revealed that the histaminergic neurons, which originate in the tuberomammillary nuclei of the posterior hypothalamus, densely innervate most of the hypothalamic areas involved in the neuroendocrine control of pituitary hormone secretion [4-5]. Within the last two decades the effect of HA on pituitary hormone secretion have been explored in several studies and it has been... 

The histamine H3 receptor was first identified as an autoreceptor (Arrang et al. 1983), negatively regulating the synthesis and release of histamine in the CNS. Release-inhibiting H3 receptors have also been identified on terminals of various other neurons in the CNS and the periphery. Hi, H2 and H4 receptors function as presynaptic receptors rarely, if ever (Schwartz et al. 1986 Tanaka and Ichikawa 2006). 

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