Histamine as Neurotransmitter
Divya Vohora in The Third Histamine Receptor, 2008
Histamine in the brain is inactivated in the extracellular space by methylation through neuronal histamine N-methyltransferase (HNMT; EC 2.1.1.8; Figure 3.1) [37]. Histamine methylation requires S-adenosyl-methionine as the methyl donor [38,39]. HNMT is also found in the walls of blood vessels where bloodborne histamine and histamine released from mast cells are methylated and inactivated [40]. Tele-methylhistamine in the brain undergoes oxidative deamination through a monoamine oxidase (MAO)-B to t-methyl-imidazoleacetic acid [39,41]. Histamine hardly passes the blood–brain barrier. The main histamine-degrading enzyme in peripheral tissues (gut, connective tissues) and invertebrates is diamine oxidase (DAO), which directly converts histamine into imidazoleacetic acid. DAO activity in the brain is negligible under basal conditions but when HNMT is inhibited, it may represent a salvage pathway for the production of imidazoleacetic acid, an effective GABAA receptor agonist [42,43].
Sympathetic Neurotransmission
Kenneth J. Broadley in Autonomic Pharmacology, 2017
A separate enzyme responsible for the deamination of histamine was initially termed histaminase but later renamed diamine oxidase (DAO; EC 1.4.3.6) to distinguish it from MAO. This is a member of a group of copper-containing enzymes which are sensitive to inhibition by semi-carbazide and hence termed semi-carbazide-sensitive amine oxidases (SSAOs). The preferred substrate of the SSAOs not deaminating histamine appears to be benzylamine. This is not a naturally occurring amine and the physiological significance remains to be established. However, SSAO enzymes do deaminate putricine, spermidine and spermine. The latter two amines are produced by herbivores from cellulose fermentation in the rumen. SSAOs may in fact serve a general role for inactivating and detoxifying dietary amines. A further distinction from MAO is the location of SSAO in smooth muscle cells of blood vessel walls, in addition to adipose tissue, and its absence from the brain. The close association with the vessel wall makes SSAO ideally suited to scavenging circulating amines. These may be endogenous amines (eg adrenaline), dietary amines or xenobiotics arising from industrial or environmental sources.
Gastrointestinal Lymphatics
Waldemar L. Olszewski in Lymph Stasis: Pathophysiology, Diagnosis and Treatment, 2019
Much of the protein in lymph is derived by filtration from plasma. A small proportion, however, is derived from local sources (see Table 3). Lipoproteins are synthesized in the enterocyte both during absorption and fasting, the major particles secreted being chylomicrons and very low density lipoproteins.77 The principal apolipoproteins synthesized in the enterocyte are apo B and apo AI, All, and AIV. In the rat, the intestine accounts for greater than 60% of the total body synthesis of apo AIV. During fat absorption alkaline phosphatase, derived from the enterocyte, is found in lymph. It seems to be related to the process of intracellular transport of lipid and/or synthesis of lipoproteins.78 The significance of the phenomenon, however, is unclear. Similarly, diamine oxidase of intestinal origin is found in lymph during absorption; again, the mechanism and significance are unknown.79
Epithelial integrity, junctional complexes, and biomarkers associated with intestinal functions
Published in Tissue Barriers, 2022
Arash Alizadeh, Peyman Akbari, Johan Garssen, Johanna Fink-Gremmels, Saskia Braber
The diamine oxidase enzyme could be detected in the apical part of villus cells and is continuously released from the intestinal mucosa, and has the ability to catalyze the deamination of histamines. Diamine oxidase enzyme levels in the blood can be used as a biomarker of intestinal permeability. Small intestinal mucosal damage may decrease the diamine oxidase activity. In addition, D-lactate, produced by many of the bacteria found in the GIT, showed enhanced levels in the circulation following intestinal damage.152–155 Recently, it has been demonstrated that D-lactate and diamine oxidase serum levels appear to be biomarkers in patients with Crohn’s disease.156 Więcek et al reported that D-lactate serum levels in patients who suffering from cystic fibrosis might be a good indicator for exocrine pancreatic insufficiency in relation to dysbiosis or overgrowth in the intestines.157
Biomarkers of immunotherapy response in patients with allergic rhinitis
Published in Expert Review of Clinical Immunology, 2018
Amelia Licari, Riccardo Castagnoli, Ilaria Brambilla, Maria Angela Tosca, Maria De Filippo, Gianluigi Marseglia, Giorgio Ciprandi
Basophil activation can be studied through flow cytometry-based assays, evaluating the expression of surface markers, such as CD63 and CD203c [41]. Moreover, a new functional assay based on intracellular staining of phycoerythrin-conjugated diamine oxidase (DAO) is available [42]. The data from the application of basophil activation during AIT in placebo-controlled trials are still conflicting. Some studies report a reduction in basophil activation following AIT that is possibly due to serological factors [43,44], while others failed to demonstrate suppression of basophil activation in successful trials of AIT [31]. A hypothesis for these contrasting findings is the different route of immunotherapy, with SLIT being possibly less effective in inhibiting basophils than SCIT. Considering the possible role of basophil activation in patients’ follow-up after AIT, several studies show that basophil activation (including DAO) decreases after AIT, with one study demonstrating persistent basophil suppression after AIT discontinuation [42,45].
Cow milk protein allergy and other common food allergies and intolerances
Published in Paediatrics and International Child Health, 2019
Wiparat Manuyakorn, Pornthep Tanpowpong
There is a high histamine content in ripened or fermented foods such as aged cheese or yeast products [65,66]. It has been proposed that reduced diamine oxidase activity causes symptoms such as urticaria, flushing, rhinorrhoea and diarrhoea. Histamine intolerance has been described in children [67], but the true prevalence is unknown. An observational study in Austria reported 31 children (mean age 8 years) who presented with chronic abdominal pain, a history of ingesting histamine-rich foods and low serum diamine oxidase related to a presumed diagnosis of histamine intolerance, but it was later found that most of the children failed to show a positive response in DBPCFC. Patients with IBS also report gastrointestinal symptoms related to histamine-rich foods [42].
Related Knowledge Centers
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