Histamine, synthesis

In 1966, the name was proposed (5) for receptors blocked by the at that time known antihistamines. It was also speculated that the other actions of histamine were likely to be mediated by other histamine receptors. The existence of the H2 receptor was accepted in 1972 (6) and the receptor was recognized in rat brain in 1983 (7). receptors in the brain appear to be involved in the feedback control of both histamine synthesis and release, whereas release of various other neurotransmitters, eg, serotinin (5-HT), dopamine, noradrenaline, and acetylcholine, is also modulated (8) (see Neuroregulators). 

Although mast cells and basophils probably account for >90% of stored histamine in the body, histamine is also present in platelets, enterochromaffin-like cells, endothelial cells, and neurons. Histamine can act as a neurotransmitter in the brain. Histaminergic nerves have their cell bodies within a very small area of the brain (the magnocellular nuclei of the posterior hypothalamus) but have axons in most areas of the forebrain. There is also evidence for axons projecting into the spinal (Fig. 1) cord. Finally, there is evidence that histamine synthesis can be induced in tissues undergoing rapid tissue growth and repair. In certain neonatal tissues (e.g. liver), the rate of synthesis of this unstored diffusable histamine (termed nascent histamine) is profound and may point to a role for histamine is cell proliferation. 

Histamine synthesis from 1-histidine can be selectively inhibited by a-fluoromethylhistidine. Metabolism by... 

Figure 13.4 Histamine synthesis, metabolism and receptors. Current knowledge does not justify presentation of a schematic histaminergic synapse. (1) Histidine decarboxylase (2) histamine-A-methyltransferase (3) mono amine oxidase (MAOb)...

Figure 6.1 Histamine synthesis and metabolism in neurons. L-histidine is transported into neurons by the L-amino acid transporter. Once inside the neuron, L-histidine is converted into histamine by the specific enzyme histidine decarboxylase. Subsequently, histamine is taken up into vesicles by the vesicular monoamine transporter and stored there until released. In the absence of a high-affinity uptake mechanism in the brain, released histamine is rapidly degraded by histamine methyltransferase, which is located postsynaptically and in glia, to telemethylhistamine, a metabolite that does not show any histamine-like activity.

Arrang, J. M., Garbarg, M. Schwartz, J. C. (1987b). Autoinhibition of histamine synthesis mediated by presynaptic H3-receptors. Neuroscience 23, 149-57. 

Specific enzymes control histamine synthesis and breakdown 253 Several forms of histidine decarboxylase may derive from a single gene 254... 

Histamine synthesis in the brain is controlled by the availability of L-histidine and the activity of histidine decarboxylase 254 Histamine is stored within and released from neurons but a neuronal transporter for histamine has not been found 254 In the vertebrate brain, histamine metabolism occurs predominately by methylation 254... 

Specific enzymes control histamine synthesis and breakdown. Figure 14-3 summarizes the major mechanisms for the synthesis and metabolism of histamine. 

Histamine synthesis in the brain is controlled by the availability of L-histidine and the activity of histidine decarboxylase. Although histamine is present in plasma, it does not penetrate the blood-brain barrier, such that histamine concentrations in the brain must be maintained by synthesis. With a value of 0.1 mmol/1 for L-histidine under physiological conditions, HDC is not saturated by histidine concentrations in the brain, an observation that explains the effectiveness of large systemic doses of this amino acid in raising the concentrations of histamine in the brain. The essential amino acid L-histidine is transported into the brain by a saturable, energy-dependent mechanism [5]. Subcellular fractionation studies show HDC to be localized in cytoplasmic fractions of isolated nerve terminals, i.e. synaptosomes. 

Gomez-Ramirez, J., Ortiz, J. and Blanco, I. Presynaptic H3 autoreceptors modulate histamine synthesis through cAMP pathway. Mol. Pharmacol. 61 239-245, 2002. 

Tanaka S. Takasu Y, Mikura S, Satoh N, Ichikawa A Antigen-independent induction of histamine synthesis by immunoglobulin E in mouse bone marrow-derived mast cells. J Exp Med 2002 196 229-235. 

Hydrocortisone exhibits anti-shock, anti-allergy, and anti-inflammatory action. It raises sugar content in the blood, increases potassium secretion, and lowers sodium excretion from the body. It exhibits anti-metaboUc action and reduces histamine synthesis in the body. 

Corbel, S., Schneider, E. and Lemoine, F. (1995) Dy, Murine hematopoietic progenitors are capable of both histamine synthesis and update. Blood, 86, 531-539. 

The effects of histamine on body tissues and organs can be diminished in four ways inhibition of histamine synthesis, inhibition of histamine release from storage granules, blockade of histamine receptors, and physiological antagonism of histamine s effects. Of these approaches, only the inhibition of histamine synthesis has not been employed clinically. The focus of this chapter is on Hi histamine receptor antagonists it provides a brief overview of the H2 blockers and the inhibitors of histamine release. More details can be found in Chapters 39 and 40. 

Suppression of lymphocyte proliferation Suppression of antibody production by B lymphocytes Relaxes stomach and gallbladder smooth muscle H3Modulation of histamine synthesis and release Inhibits vagally mediated bronchoconstriction Vasodilatation... 

The H3 receptor was initially detected as an autoreceptor controlling histamine synthesis and release in brain [22]. Thereafter it was shown to inhibit presynaptically the release of other monoamines in brain and peripheral tissues as well as of neuropeptides from unmyelinated C-fibers [23],... 

In addition to histamine release, histamine synthesis is also inhibited presynaptically by histamine, and the H3 receptor is linked to this effect [31]. In the cerebral cortex of rats injected with the radiolabelled precursor of histamine, [3H]L-histidine, [3H]histamine synthesis decreased significantly in a dose-dependent manner after systemic administration of RAMH [25]. This inhibition could be reversed by intraperitoneal administration of thioperamide [18, 25]. Interestingly, administration of thioperamide alone produced a marked increase in histamine synthesis, indicative of the presence of a degree of tonic inhibition elicited by H3-receptors [18]. 

Figure 3. Effect of N -methylhistamine produced by Helicobacter pylori on acid secretion On the one hand, this compound may reduce acid secretion by inhibiting, via H3 receptor activation, histamine synthesis and release from ECL cells on the other hand, FI3 receptor activation on D cells, with consequent inhibition of somatostatin release, may increase acid secretion. Additionally, direct activation of H2 receptors on parietal cell by N -metylhistamine must also be considered (this mechanism is not shown in the scheme).

H3 receptor activation in the airway system of the guinea pig caused a decrease in histamine release from mast cell and/or basophils and the H3 antagonist had the opposite effect. As far as histamine synthesis is concerned, the allergen-exposure induced histamine forming capacity could be increased by thioperamide, even though (R)a-methylhistamine was completely inactive. The explanation given for this peculiar phenomenon was that the histamine... 

Hollande, F., Bali, J.P., Magous, R., 1993. Autoregulation of histamine synthesis through H3 receptors in isolated fimdic mucosal cells. Am. J. Physiol. 265, G1039-G1044... 

Modulation of histamine synthesis and release in brain via presynaptic autoreceptors and heteroreceptors. In Presynaptic receptors and the question of autoregulation of neurotransmitter release Kalsner, S.,Westfall T.C. Eds. Annals of the New York Academy of Sciences New York, 1991 Vol. 604 pp. 40-54. 

Early events — release of histamine, synthesis of cyclic adenosine monophosphate (cyclic AMP), stimulation of RNA polymerase, and increased excitability of the myometrium. 

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 liber 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. 

Apart from exocytosis, presynaptic H3 autoreceptors also inhibit the synthesis of histamine at the level of nerve endings, at least in part through pathways distinct from those leading to the inhibition of release. One pathway is inhibition of adenylyl cyclase (Gomez-Ramirez et al. 2002 Moreno-Delgado et al. 2006) activation of cAMP-dependent protein kinase A by cAMP stimulates histamine synthesis through phosphorylation of histidine decarboxylase, and this stimulation is diminished when adenylyl cyclase activity decreases following activation of H3 autoreceptors and Gi/o proteins. 

Gomez-Ramirez J, Ortiz J, Blanco I (2002) Presynaptic H3 autoreceptors modulate histamine synthesis through cAMP pathway. Mol Pharmacol 61 239-45 Goncalves J, Bultmann R, Driessen B (1996) Opposite modulation of cotransmitter release in guinea pig vas deferens increase of noradrenaline and decrease of ATP release by activation of prejunctional beta-adrenoceptors. Naunyn-Schmiedeberg s Arch Pharmacol 353 184-92 Gonzalez-Islas C, Hablitz J (2001) Dopamine inhibition of evoked IPSCs in rat prefrontal cortex. J Neurophysiol 86 2911-18... 

Mooney RD, Shi MY, Rhoades RW (1994) Modulation of retinotectal transmission by presynaptic 5-HTib receptors in the superior colliculus of the adult hamster. J Neurophysiol 72 3-13 Moreno-Delgado D, Torrent A, Gomez-Ramirez J, de Esch I, Blanco I, Ortiz J (2006) Constitutive activity of H3 autoreceptors modulates histamine synthesis in rat brain through the cAMP/PKA pathway. Neuropharmacology 51 517-23... 

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