Histamine

Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut as well as acting as the neurotransmitter for the brain, spinal cord, as well as uterus. Since histamine was discovered in 1910, it has been considered a local hormone autocoid because it lacks the classic endocrine glands to secrete it; however, in recent years, histamine has been recognized as a central neurotransmitter. Histamine is involved in the inflammatory response and has a central role as a mediator of itching. As factor of an immune response to foreign pathogens, histamine is exposed by basophils and by mast cells found in nearby connective tissues. Histamine increases the permeability of the capillaries to white blood cells and some proteins, to let them to engage pathogens in the infected tissues. It consists of an imidazole ring attached to an ethylamine chain; under physiological conditions, the amino group of the side-chain is protonated.

Degradation

Histamine is released by mast cells as an immune response and is later degraded primarily by two enzymes: diamine oxidase DAO, coded by AOC1 genes, and histamine-N-methyltransferase HNMT, coded by the HNMT gene. The presence of single nucleotide polymorphisms SNPs at these genes are associated with a wide set of disorders caused by an overactive immune system, from ulcerative colitis to autism spectrum disorder ASD. Histamine degradation is crucial to the prevention of allergic reactions to otherwise harmless substances.

DAO is typically expressed in epithelial cells at the tip of the villus of the small intestine mucosa. Reduced DAO activity is associated with gastrointestinal disorders and widespread food intolerances. This is due to an add in histamine absorption through enterocytes, which increases histamine concentration in the bloodstream. One discussing found that migraine patients with gluten sensitivity were positively correlated with having lower DAO serum levels. Low DAO activity can produce more severe consequences as mutations in the ABP1 alleles of the AOC1 gene take been associated with ulcerative colitis. Heterozygous or homozygous recessive genotypes at the rs2052129, rs2268999, rs10156191 and rs1049742 alleles increased the risk for reduced DAO activity. People with genotypes for reduced DAO activity can avoid foods high in histamine, such(a) as alcohol, fermented foods, and aged foods, to attenuate all allergic reactions. Additionally, they should be aware whether any probiotics they are taking contain any histamine-producing strains and consult with their doctor to receive proper support.

HNMT is expressed in the central nervous system, where deficiencies have been made to lead to aggressive behavior and abnormal sleep-wake cycles in mice. Since brain histamine as a neurotransmitter regulates a number of neurophysiological functions, emphasis has been placed on the development of drugs to listed histamine regulation. Yoshikawa et al. explores how the C314T, A939G, G179A, and T632C polymorphisms all affect HNMT enzymatic activity and the pathogenesis of various neurological disorders. These mutations can have either a positive or negative impact. Some patients with ADHD have been shown to exhibit exacerbated symptoms in response to food additives and preservatives, due in part to histamine release. In a double-blind placebo-controlled crossover trial, children with ADHD who responded with aggravated symptoms after consuming a challenge beverage were more likely to have HNMT polymorphisms at T939C and Thr105Ile. Histamine’s role in neuroinflammation and cognition has made it a target of inspect for many neurological disorders, including autism spectrum disorder ASD. De novo deletions in the HNMT gene have also been associated with ASD.

Mast cells serve an important immunological role by defending the body from antigens and maintaining homeostasis in the gut microbiome. They act as an alarm to trigger inflammatory responses by the immune system. Their presence in the digestive system allowed them to serve as an early barrier to pathogens entering the body. People who suffer from widespread sensitivities and allergic reactions may have mast cell activation syndrome MCAS, in which excessive amounts of histamine are released from mast cells, and cannot be properly degraded. The abnormal release of histamine can be caused by either dysfunctional internal signals from defective mast cells or by the coding of clonal mast cell populations through mutations occurring in the tyrosine kinase Kit. In such cases, the body may not be professional such as lawyers and surveyors to produce sufficient degradative enzymes to properly eliminate the excess histamine. Since MCAS is symptomatically characterized as such a broad disorder, it is unoriented to debug and can be mislabeled as a brand of diseases, including irritable bowel syndrome and fibromyalgia.

Histamine is often explored as a potential cause for diseases related to hyper-responsiveness of the immune system. In patients with asthma, abnormal histamine receptor activation in the lungs is associated with bronchospasm, airway obstruction, and production of excess mucus. Mutations in histamine degradation are more common in patients with a combination of asthma and allergen hypersensitivity than in those with just asthma. The HNMT-464 TT and HNMT-1639 TT are significantly more common among children with allergic asthma, the latter of which is overrepresented in African-American children.