Histamine: New Thoughts About a Familiar Mediator

Bl, Jones; Kearns, G. L.

doi:10.1038/clpt.2010.256

“…Rescue of the behavioral phenotype of spd mutants with the Hrh3 agonist imetit (Garbarg et al, 1992) provides evidence that Hrh3 may underlie these behaviors, although we cannot explicitly rule out a contribution of Hrh1 and Hrh2 activity as well. Hrh3 acts as both an autoreceptor and a heteroreceptor (Peitsaro et al, 2000) and has a complex role in the control of HA neurotransmission (Leurs et al, 2005;Jones and Kearns, 2011). Hrh3 knock-out mice have a net decrease of HA levels in the cortex (Toyota et al, 2002) and show reduced anxiety in an elevated plus maze (Rizk et al, 2004) reminiscent of the spd phenotype.…”

Section: Discussionmentioning

confidence: 99%

Modulation of Fgfr1a Signaling in Zebrafish Reveals a Genetic Basis for the Aggression–Boldness Syndrome

Norton¹,

Stumpenhorst²,

et al. 2011

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Behavioral syndromes are suites of two or more behaviors that correlate across environmental contexts. The aggression-boldness syndrome links aggression, boldness, and exploratory activity in a novel environment. Although aggression-boldness has been described in many animals, the mechanism linking its behavioral components is not known. Here we show that mutation of the gene encoding fibroblast growth factor receptor 1a ( fgfr1a) simultaneously increases aggression, boldness, and exploration in adult zebrafish. We demonstrate that altered Fgf signaling also results in reduced brain histamine levels in mutants. Pharmacological increase of histamine signaling is sufficient to rescue the behavioral phenotype of fgfr1a mutants. Together, we show that a single genetic locus can underlie the aggression-boldness behavioral syndrome. We also identify one of the neurotransmitter pathways that may mediate clustering of these behaviors.

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“…The synthesis of histamine begins with the alpha-decarboxylation of L-histidine by the enzyme histadine decarboxylase (HDC) [6,17] [10]. Activation of HR2 is commonly known to increase gastric acid secretion.…”

Section: Introductionmentioning

confidence: 99%

“…However, it also is involved in smooth muscle relaxation, airway mucus production, and inhibition of histamine release from basophils and mast cells [19][20][21]. HR3 is expressed in the central and peripheral nervous system as a presynaptic receptor controlling the release of histamine and neurotransmitters in the human brain [10,19,[22][23][24]. The HR3 receptor has been linked to satiety, sleep, and cognition [10,25,26].…”

Section: Introductionmentioning

confidence: 99%

“…In the lungs, histamine receptor activation results in bronchospasm and airway obstruction. Plasma histamine levels have been found to correlate with asthma severity [7,8] and histamine receptor activation results in increased vascular permeability, mucus production, and contraction of airway smooth muscle cell [9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

“…HR3 is expressed in the central and peripheral nervous system as a presynaptic receptor controlling the release of histamine and neurotransmitters in the human brain [10,19,[22][23][24]. The HR3 receptor has been linked to satiety, sleep, and cognition [10,25,26]. HR4 is expressed in the bone marrow, and peripheral blood hematopoietic cells such as neutrophils, eosinophils, monocytes, and T cells [27].…”

Section: Introductionmentioning

confidence: 99%

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Genetic Variation Along The Histamine Pathway In Children With Allergic Vs. Non-Allergic Asthma

Anvari

¹

,

Vyhlidal

²

,

Rezaiekhaligh

³

et al. 2014

Journal of Allergy and Clinical Immunology

0

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ABSTRACT:Rationale: Previous studies have suggested that antihistamines may be therapeutic in some patients with asthma. Variation in genes along the histamine production, response, and degradation pathway may be important in predicting response to antihistamines. We hypothesize that genetic variation in genes of the histamine pathway differs between children with allergic versus non-allergic asthma.Methods: Children 7-18 years of age (n=118) with asthma participated in this IRB-approved protocol and were classified as allergic (N = 68) or non-allergic (N = 50) based on allergy skin testing. DNA isolation and genotyping were performed for 10 SNPs within 4 genes (HDC, HNMT, ABP1, HRH1, HRH4) within the histamine pathway. Chi Square tests were used to test for associations between genotypes and allergic or non-allergic asthma among participants.Significance was determined by p <0.05. Results:We observed differences in genotype frequency between participants with allergic versus non-allergic asthma for 2 SNPs: HNMT-1639(rs6430764) (31% allergic with TT vs. 14% non-allergic with TT, p=0.04) and HNMT -464 (rs2071048) genotype (33% allergic with TT vs.12% non-allergic with TT, p=0.03) after controlling for race. Differences in genotype frequency were also observed between allergic and non-allergic phenotypes in stratified analyses among African Americans. Conclusion:Genetic variants within the histamine pathway appear to be associated with an allergic versus non-allergic asthma phenotype. Further studies are needed to validate our findings in a larger cohort. There is also the need to determine the functional significance of identified SNPs and their impact on antihistamine response in patients with asthma and allergic disease. iv ACKNOWLEDGMENTS:

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Histamine Biosynthesis and Function

Ichikawa

¹

,

Tanaka

²

2012

Encyclopedia of Life Sciences

1

0

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Histamine is one of the essential biogenic amines that mediate a wide variety of physiological and pathological responses, such as inflammation, gastric acid secretion, neurotransmission and immune modulation. Histamine is synthesised through decarboxylation of l ‐histidine and functions by acting on its specific receptors consisting of H 1 , H 2 , H 3 and H 4 subtypes. Mast cells and basophils store histamine in their cytoplasmic granules and release it when stimulated, whereas histamine release is closely associated with its de novo synthesis in gastric enterochromaffin‐like cells, and neurons. A series of antagonists targeting H 1 and H 2 subtype has brought about enormous success to therapies for immediate allergy and peptic ulcer, respectively. The H 3 subtype has been focused on as the therapeutic target for cognitive dysfunctions, because it is expressed preferentially in neurons and modulates the neurotransmitter release. Recently identified H 4 subtype is expressed preferentially in blood cells and mediates their chemotaxis in response to histamine. Key Concepts: Histamine mediates a wide variety of physiological and pathological responses, such as inflammation, gastric acid secretion, neurotransmission and immune modulation. Histamine is synthesised through decarboxylation of l ‐histidine by histidine decarboxylase and is catabolised through oxidative deamination or methylation. Tissue histamine levels are transiently increased by degranulation of mast cells and basophils while they are upregulated by de novo synthesis in gastric enterochromaffin‐like cells, and neurons. Histamine exerts its functions by acting on its specific receptors consisting of H 1 , H 2 , H 3 and H 4 receptors. Histamine is a paracrine mediator, of which actions are generally limited in the local microenvironment. Histamine H 1 receptor antagonists have brought successful therapeutic approaches for immediate allergy, because histamine evokes vasodilation and increased vascular permeability by acting on the H 1 receptor. In the central nervous system, histamine is involved in awakening, appetite, maintenance of circadian rhythm, learning and memory, which are regulated by the H 1 and H 3 receptors. Histamine stimulates parietal cells to induce gastric acid secretion by acting on the H 2 receptor, of which antagonists drastically improved therapeutic approaches for peptic ulcer. Pre‐synaptic histamine H 3 receptor regulates release of various neurotransmitters including histamine itself, and is expected as a potential drug target for the treatment of cognitive dysfunctions. Histamine H 4 receptor is expressed exclusively in blood cells and mediates their chemotaxis in response to histamine.

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Histamine: New Thoughts About a Familiar Mediator

Cited by 64 publications

References 50 publications

Modulation of Fgfr1a Signaling in Zebrafish Reveals a Genetic Basis for the Aggression–Boldness Syndrome

Modulation of Fgfr1a Signaling in Zebrafish Reveals a Genetic Basis for the Aggression–Boldness Syndrome

Genetic Variation Along The Histamine Pathway In Children With Allergic Vs. Non-Allergic Asthma

Histamine Biosynthesis and Function

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