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Open AccessEditorial

New Insight in Histamine Functions

by Silvia Sgambellone, Silvia Marri, Emanuela Masini and Laura Lucarini

Biomolecules 2022, 12(5), 609; https://doi.org/10.3390/biom12050609 - 19 Apr 2022

Cited by 1 | Viewed by 2358

Abstract

The first properties of histamine (HA) that were elucidated were vasodilation and contraction of smooth muscles in the gut after stimulating gastric acid secretion and constriction of the bronchial area during anaphylaxis [...] Full article

(This article belongs to the Special Issue New Developments in Histamine Research)

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13 pages, 3409 KiB

Open AccessEditor’s ChoiceArticle

CNS-Sparing Histamine H₃ Receptor Antagonist as a Candidate to Prevent the Diabetes-Associated Gastrointestinal Symptoms

by Arianna Carolina Rosa, Patrizia Nardini, Silvia Sgambellone, Maura Gurrieri, Simona Federica Spampinato, Alfonso Dell’Accio, Paul L Chazot, Ilona Obara, Wai L Liu and Alessandro Pini

Biomolecules 2022, 12(2), 184; https://doi.org/10.3390/biom12020184 - 22 Jan 2022

Cited by 6 | Viewed by 3585

Abstract

Among the histamine receptors, growing evidence points to the histamine H₃ receptor as a pharmacological candidate to counteract the autonomic neuropathy associated with diabetes. The study aimed to evaluate the effect of PF00868087 (also known as ZPL-868), a CNS-sparing histamine H₃ [...] Read more.

Among the histamine receptors, growing evidence points to the histamine H₃ receptor as a pharmacological candidate to counteract the autonomic neuropathy associated with diabetes. The study aimed to evaluate the effect of PF00868087 (also known as ZPL-868), a CNS-sparing histamine H₃ receptor antagonist, on the autonomic neuropathy of the intestinal tract associated with diabetes. Diabetes was induced in male BALB/c mice by a single high dose of streptozotocin (150 mg/kg). Colorectal specimens from control and diabetic mice, randomized to vehicle or PF0086087 (10, 30, 100 mg/kg/day by oral gavage for 14 days), were processed for morphological and immunohistochemical analysis. A significant overproduction of mucus in the intestinal mucosa of diabetic mice compared to the controls was observed. PF0086087 at the highest dose prevented mucin overproduction. The immunohistochemistry analysis demonstrated that diabetes causes a decrease in the inhibitory component of enteric motility, measured as the percentage of neuronal nitric oxide synthase-positive neurons (p < 0.05) and a parallel increase in the excitatory component evaluated as substance P-positive fibres (p < 0.01). PF0086087 dose-dependently prevented these pathophysiological events. In conclusion, PF0086087 may be an essential tool in preventing nitrergic dysfunction in the myenteric plexus of the distal colon and diabetes-induced gastrointestinal complications. Full article

(This article belongs to the Special Issue New Developments in Histamine Research)

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19 pages, 4981 KiB

Open AccessArticle

The Interplay between Histamine H₄ Receptor and the Kidney Function: The Lesson from H₄ Receptor Knockout Mice

by Roberta Verta, Maura Gurrieri, Sara Borga, Elisa Benetti, Paolo Pollicino, Roberta Cavalli, Robin L. Thurmond, Paul L. Chazot, Alessandro Pini, Arianna Carolina Rosa and Cristina Grange

Biomolecules 2021, 11(10), 1517; https://doi.org/10.3390/biom11101517 - 15 Oct 2021

Cited by 2 | Viewed by 3500

Abstract

Previous studies implicated the histamine H₄ receptor in renal pathophysiology. The aim here is to elucidate the role of this receptor on renal function using H₄ receptor knockout mice (H₄R^−/−). Healthy and diabetic H₄R^−/− [...] Read more.

Previous studies implicated the histamine H₄ receptor in renal pathophysiology. The aim here is to elucidate the role of this receptor on renal function using H₄ receptor knockout mice (H₄R^−/−). Healthy and diabetic H₄R^−/− mice compared to their C57BL/6J wild-type counterpart for renal function and the expression of crucial tubular proteins. H₄R^−/− and wild-type mice, matched for ages, showed comparable weight gain curves reaching similar median weight at the end of the study. However, H₄R^−/− mice displayed a higher basal glycemia. H₄R^−/− mice showed a lower urine 24 h outflow, and albumin-to-creatinine ratio (ACR) compared to wild-type mice. Consistently, H₄R^−/− mice presented a higher expression of megalin and a lower basal expression of the sodium-hydrogen exchanger (NHE)3 and aquaporin (AQP)2. According to these basal differences, diabetic H₄R^−/− mice developed more severe hyperglycemia and a higher 24 h urine volume, but a lower increase in ACR and decrease in urine pH were observed. These events were paralleled by a reduced NHE3 over-expression and megalin loss in diabetic H₄R^−/− mice. The AQP1 and AQP7 patterns were also different between H₄R^−/− and wild-type diabetic mice. The collected results highlight the role of the histamine H₄ receptor in the control of renal reabsorption processes, particularly albumin uptake. Full article

(This article belongs to the Special Issue New Developments in Histamine Research)

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11 pages, 1770 KiB

Open AccessArticle

The Histamine H₄ Receptor Participates in the Anti-Neuropathic Effect of the Adenosine A₃ Receptor Agonist IB-MECA: Role of CD4⁺ T Cells

by Laura Micheli, Mariaconcetta Durante, Elena Lucarini, Silvia Sgambellone, Laura Lucarini, Lorenzo Di Cesare Mannelli, Carla Ghelardini and Emanuela Masini

Biomolecules 2021, 11(10), 1447; https://doi.org/10.3390/biom11101447 - 2 Oct 2021

Cited by 10 | Viewed by 2422

Abstract

A₃ adenosine receptor (A₃AR) agonists have emerged as potent relievers of neuropathic pain by a T cell-mediated production of IL-10. The H₄ histamine receptor (H₄R), also implicated in pain modulation, is expressed on T cells playing a [...] Read more.

A₃ adenosine receptor (A₃AR) agonists have emerged as potent relievers of neuropathic pain by a T cell-mediated production of IL-10. The H₄ histamine receptor (H₄R), also implicated in pain modulation, is expressed on T cells playing a preeminent role in its activation and release of IL-10. To improve the therapeutic opportunities, this study aimed to verify the hypothesis of a possible cross-talk between A₃AR and H₄R in the resolution of neuropathic pain. In the mouse model of Chronic Constriction Injury (CCI), the acute intraperitoneal co-administration of the A₃AR agonist IB-MECA (0.5 mg/kg) and the H₄R agonist VUF 8430 (10 mg/kg), were additive in counteracting mechano-allodynia increasing IL-10 plasma levels. In H₄R^−/− mice, IB-MECA activity was reduced, lower pain relief and lower modulation of plasma IL-1β, TNF-α, IL-6 and IL-10 were shown. The complete anti-allodynia effect of IB-MECA in H₄R^−/− mice was restored after intravenous administration of CD4⁺ T cells obtained from naïve wild type mice. In conclusion, a role of the histaminergic system in the mechanism of A₃AR-mediated neuropathic pain relief was suggested highlighting the driving force evoked by CD4⁺ T cells throughout IL-10 up-regulation. Full article

(This article belongs to the Special Issue New Developments in Histamine Research)

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16 pages, 8524 KiB

Open AccessArticle

TRPV1 and TRPA1 Channels Are Both Involved Downstream of Histamine-Induced Itch

by Jenny Wilzopolski, Manfred Kietzmann, Santosh K. Mishra, Holger Stark, Wolfgang Bäumer and Kristine Rossbach

Biomolecules 2021, 11(8), 1166; https://doi.org/10.3390/biom11081166 - 6 Aug 2021

Cited by 31 | Viewed by 4891

Abstract

Two histamine receptor subtypes (HR), namely H1R and H4R, are involved in the transmission of histamine-induced itch as key components. Although exact downstream signaling mechanisms are still elusive, transient receptor potential (TRP) ion channels play important roles in the sensation of histaminergic and [...] Read more.

Two histamine receptor subtypes (HR), namely H1R and H4R, are involved in the transmission of histamine-induced itch as key components. Although exact downstream signaling mechanisms are still elusive, transient receptor potential (TRP) ion channels play important roles in the sensation of histaminergic and non-histaminergic itch. The aim of this study was to investigate the involvement of TRPV1 and TRPA1 channels in the transmission of histaminergic itch. The potential of TRPV1 and TRPA1 inhibitors to modulate H1R- and H4R-induced signal transmission was tested in a scratching assay in mice in vivo as well as via Ca²⁺ imaging of murine sensory dorsal root ganglia (DRG) neurons in vitro. TRPV1 inhibition led to a reduction of H1R- and H4R- induced itch, whereas TRPA1 inhibition reduced H4R- but not H1R-induced itch. TRPV1 and TRPA1 inhibition resulted in a reduced Ca²⁺ influx into sensory neurons in vitro. In conclusion, these results indicate that both channels, TRPV1 and TRPA1, are involved in the transmission of histamine-induced pruritus. Full article

(This article belongs to the Special Issue New Developments in Histamine Research)

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16 pages, 10498 KiB

Open AccessArticle

Identification of TSPAN4 as Novel Histamine H₄ Receptor Interactor

by Xiaoyuan Ma, Eléonore W. E. Verweij, Marco Siderius, Rob Leurs and Henry F. Vischer

Biomolecules 2021, 11(8), 1127; https://doi.org/10.3390/biom11081127 - 30 Jul 2021

Cited by 8 | Viewed by 3610

Abstract

The histamine H₄ receptor (H₄R) is a G protein-coupled receptor that is predominantly expressed on immune cells and considered to be an important drug target for various inflammatory disorders. Like most GPCRs, the H₄R activates G proteins and [...] Read more.

The histamine H₄ receptor (H₄R) is a G protein-coupled receptor that is predominantly expressed on immune cells and considered to be an important drug target for various inflammatory disorders. Like most GPCRs, the H₄R activates G proteins and recruits β-arrestins upon phosphorylation by GPCR kinases to induce cellular signaling in response to agonist stimulation. However, in the last decade, novel GPCR-interacting proteins have been identified that may regulate GPCR functioning. In this study, a split-ubiquitin membrane yeast two-hybrid assay was used to identify H₄R interactors in a Jurkat T cell line cDNA library. Forty-three novel H₄R interactors were identified, of which 17 have also been previously observed in MYTH screens to interact with other GPCR subtypes. The interaction of H₄R with the tetraspanin TSPAN4 was confirmed in transfected cells using bioluminescence resonance energy transfer, bimolecular fluorescence complementation, and co-immunoprecipitation. Histamine stimulation reduced the interaction between H₄R and TSPAN4, but TSPAN4 did not affect H₄R-mediated G protein signaling. Nonetheless, the identification of novel GPCR interactors by MYTH is a starting point to further investigate the regulation of GPCR signaling. Full article

(This article belongs to the Special Issue New Developments in Histamine Research)

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23 pages, 4739 KiB

Open AccessArticle

Histamine Ingestion by Anopheles stephensi Alters Important Vector Transmission Behaviors and Infection Success with Diverse Plasmodium Species

by Anna M. Rodriguez, Malayna G. Hambly, Sandeep Jandu, Raquel Simão-Gurge, Casey Lowder, Edwin E. Lewis, Jeffrey A. Riffell and Shirley Luckhart

Biomolecules 2021, 11(5), 719; https://doi.org/10.3390/biom11050719 - 11 May 2021

Cited by 10 | Viewed by 3453

Abstract

An estimated 229 million people worldwide were impacted by malaria in 2019. The vectors of malaria parasites (Plasmodium spp.) are Anopheles mosquitoes, making their behavior, infection success, and ultimately transmission of great importance. Individuals with severe malaria can exhibit significantly increased blood [...] Read more.

An estimated 229 million people worldwide were impacted by malaria in 2019. The vectors of malaria parasites (Plasmodium spp.) are Anopheles mosquitoes, making their behavior, infection success, and ultimately transmission of great importance. Individuals with severe malaria can exhibit significantly increased blood concentrations of histamine, an allergic mediator in humans and an important insect neuromodulator, potentially delivered to mosquitoes during blood-feeding. To determine whether ingested histamine could alter Anopheles stephensi biology, we provisioned histamine at normal blood levels and at levels consistent with severe malaria and monitored blood-feeding behavior, flight activity, antennal and retinal responses to host stimuli and lifespan of adult female Anopheles stephensi. To determine the effects of ingested histamine on parasite infection success, we quantified midgut oocysts and salivary gland sporozoites in mosquitoes infected with Plasmodium yoelii and Plasmodium falciparum. Our data show that provisioning An. stephensi with histamine at levels consistent with severe malaria can enhance mosquito behaviors and parasite infection success in a manner that would be expected to amplify parasite transmission to and from human hosts. Such knowledge could be used to connect clinical interventions by reducing elevated histamine to mitigate human disease pathology with the delivery of novel lures for improved malaria control. Full article

(This article belongs to the Special Issue New Developments in Histamine Research)

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19 pages, 4256 KiB

Open AccessArticle

Short- and Long-Term Social Recognition Memory Are Differentially Modulated by Neuronal Histamine

by Barbara Rani, Bruna Silva-Marques, Rob Leurs, Maria Beatrice Passani, Patrizio Blandina and Gustavo Provensi

Biomolecules 2021, 11(4), 555; https://doi.org/10.3390/biom11040555 - 9 Apr 2021

Cited by 17 | Viewed by 3216

Abstract

The ability of recognizing familiar conspecifics is essential for many forms of social interaction including reproduction, establishment of dominance hierarchies, and pair bond formation in monogamous species. Many hormones and neurotransmitters have been suggested to play key roles in social discrimination. Here we [...] Read more.

The ability of recognizing familiar conspecifics is essential for many forms of social interaction including reproduction, establishment of dominance hierarchies, and pair bond formation in monogamous species. Many hormones and neurotransmitters have been suggested to play key roles in social discrimination. Here we demonstrate that disruption or potentiation of histaminergic neurotransmission differentially affects short (STM) and long-term (LTM) social recognition memory. Impairments of LTM, but not STM, were observed in histamine-deprived animals, either chronically (Hdc^−/− mice lacking the histamine-synthesizing enzyme histidine decarboxylase) or acutely (mice treated with the HDC irreversible inhibitor α-fluoromethylhistidine). On the contrary, restriction of histamine release induced by stimulation of the H₃R agonist (VUF16839) impaired both STM and LTM. H₃R agonism-induced amnesic effect was prevented by pre-treatment with donepezil, an acetylcholinesterase inhibitor. The blockade of the H₃R with ciproxifan, which in turn augmented histamine release, resulted in a procognitive effect. In keeping with this hypothesis, the procognitive effect of ciproxifan was absent in both Hdc^−/− and αFMH-treated mice. Our results suggest that brain histamine is essential for the consolidation of LTM but not STM in the social recognition test. STM impairments observed after H₃R stimulation are probably related to their function as heteroreceptors on cholinergic neurons. Full article

(This article belongs to the Special Issue New Developments in Histamine Research)

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20 pages, 2246 KiB

Open AccessArticle

Simultaneous Blockade of Histamine H₃ Receptors and Inhibition of Acetylcholine Esterase Alleviate Autistic-Like Behaviors in BTBR T+ tf/J Mouse Model of Autism

by Nermin Eissa, Petrilla Jayaprakash, Holger Stark, Dorota Łażewska, Katarzyna Kieć-Kononowicz and Bassem Sadek

Biomolecules 2020, 10(9), 1251; https://doi.org/10.3390/biom10091251 - 28 Aug 2020

Cited by 27 | Viewed by 4266

Abstract

Autism spectrum disorder (ASD) is a heterogenous neurodevelopmental disorder defined by persistent deficits in social interaction and the presence of patterns of repetitive and restricted behaviors. The central neurotransmitters histamine (HA) and acetylcholine (ACh) play pleiotropic roles in physiological brain functions that include [...] Read more.

Autism spectrum disorder (ASD) is a heterogenous neurodevelopmental disorder defined by persistent deficits in social interaction and the presence of patterns of repetitive and restricted behaviors. The central neurotransmitters histamine (HA) and acetylcholine (ACh) play pleiotropic roles in physiological brain functions that include the maintenance of wakefulness, depression, schizophrenia, epilepsy, anxiety and narcolepsy, all of which are found to be comorbid with ASD. Therefore, the palliative effects of subchronic systemic treatment using the multiple-active test compound E100 with high H₃R antagonist affinity and AChE inhibitory effect on ASD-like behaviors in male BTBR T+tf/J (BTBR) mice as an idiopathic ASD model were assessed. E100 (5, 10 and 15 mg/kg, i.p.) dose-dependently palliated social deficits of BTBR mice and significantly alleviated the repetitive/compulsive behaviors of tested animals. Moreover, E100 modulated disturbed anxiety levels, but failed to modulate hyperactivity parameters, whereas the reference AChE inhibitor donepezil (DOZ, one milligram per kilogram) significantly obliterated the increased hyperactivity measures of tested mice. Furthermore, E100 mitigated the increased levels of AChE activity in BTBR mice with observed effects comparable to that of DOZ and significantly reduced the number of activated microglial cells compared to the saline-treated BTBR mice. In addition, the E100-provided effects on ASD-like parameters, AChE activity, and activated microglial cells were entirely reversed by co-administration of the H₃R agonist (R)-α-methylhistamine (RAM). These initial overall results observed in an idiopathic ASD mice model show that E100 (5 mg/kg) alleviated the assessed behavioral deficits and demonstrate that simultaneous targeting of brain histaminergic and cholinergic neurotransmissions is crucial for palliation of ASD-like features, albeit further in vivo assessments on its effects on brain levels of ACh as well as HA are still needed. Full article

(This article belongs to the Special Issue New Developments in Histamine Research)

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Review

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16 pages, 848 KiB

Open AccessReview

The Histaminergic System in Neuropsychiatric Disorders

by Li Cheng, Jiaying Liu and Zhong Chen

Biomolecules 2021, 11(9), 1345; https://doi.org/10.3390/biom11091345 - 11 Sep 2021

Cited by 21 | Viewed by 5150

Abstract

Histamine does not only modulate the immune response and inflammation, but also acts as a neurotransmitter in the mammalian brain. The histaminergic system plays a significant role in the maintenance of wakefulness, appetite regulation, cognition and arousal, which are severely affected in neuropsychiatric [...] Read more.

Histamine does not only modulate the immune response and inflammation, but also acts as a neurotransmitter in the mammalian brain. The histaminergic system plays a significant role in the maintenance of wakefulness, appetite regulation, cognition and arousal, which are severely affected in neuropsychiatric disorders. In this review, we first briefly describe the distribution of histaminergic neurons, histamine receptors and their intracellular pathways. Next, we comprehensively summarize recent experimental and clinical findings on the precise role of histaminergic system in neuropsychiatric disorders, including cell-type role and its circuit bases in narcolepsy, schizophrenia, Alzheimer’s disease, Tourette’s syndrome and Parkinson’s disease. Finally, we provide some perspectives on future research to illustrate the curative role of the histaminergic system in neuropsychiatric disorders. Full article

(This article belongs to the Special Issue New Developments in Histamine Research)

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26 pages, 1588 KiB

Open AccessEditor’s ChoiceReview

Pathophysiological Roles of Histamine Receptors in Cancer Progression: Implications and Perspectives as Potential Molecular Targets

by Phuong Linh Nguyen and Jungsook Cho

Biomolecules 2021, 11(8), 1232; https://doi.org/10.3390/biom11081232 - 18 Aug 2021

Cited by 29 | Viewed by 11416

Abstract

High levels of histamine and histamine receptors (HRs), including H1R~H4R, are found in many different types of tumor cells and cells in the tumor microenvironment, suggesting their involvement in tumor progression. This review summarizes the latest evidence demonstrating the pathophysiological roles of histamine [...] Read more.

High levels of histamine and histamine receptors (HRs), including H1R~H4R, are found in many different types of tumor cells and cells in the tumor microenvironment, suggesting their involvement in tumor progression. This review summarizes the latest evidence demonstrating the pathophysiological roles of histamine and its cognate receptors in cancer biology. We also discuss the novel therapeutic approaches of selective HR ligands and their potential prognostic values in cancer treatment. Briefly, histamine is highly implicated in cancer development, growth, and metastasis through interactions with distinct HRs. It also regulates the infiltration of immune cells into the tumor sites, exerting an immunomodulatory function. Moreover, the effects of various HR ligands, including H1R antagonists, H2R antagonists, and H4R agonists, on tumor progression in many different cancer types are described. Interestingly, the expression levels of HR subtypes may serve as prognostic biomarkers in several cancers. Taken together, HRs are promising targets for cancer treatment, and HR ligands may offer novel therapeutic potential, alone or in combination with conventional therapy. However, due to the complexity of the pathophysiological roles of histamine and HRs in cancer biology, further studies are warranted before HR ligands can be introduced into clinical settings. Full article

(This article belongs to the Special Issue New Developments in Histamine Research)

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10 pages, 1173 KiB

Open AccessReview

Novel Insight of Histamine and Its Receptor Ligands in Glaucoma and Retina Neuroprotection

by Silvia Sgambellone, Laura Lucarini, Cecilia Lanzi and Emanuela Masini

Biomolecules 2021, 11(8), 1186; https://doi.org/10.3390/biom11081186 - 11 Aug 2021

Cited by 3 | Viewed by 3090

Abstract

Glaucoma is a multifactorial neuropathy characterized by increased intraocular pressure (IOP), and it is the second leading cause of blindness worldwide after cataracts. Glaucoma combines a group of optic neuropathies characterized by the progressive degeneration of retinal ganglionic cells (RGCs). Increased IOP and [...] Read more.

Glaucoma is a multifactorial neuropathy characterized by increased intraocular pressure (IOP), and it is the second leading cause of blindness worldwide after cataracts. Glaucoma combines a group of optic neuropathies characterized by the progressive degeneration of retinal ganglionic cells (RGCs). Increased IOP and short-term IOP fluctuation are two of the most critical risk factors in glaucoma progression. Histamine is a well-characterized neuromodulator that follows a circadian rhythm, regulates IOP and modulates retinal circuits and vision. This review summarizes findings from animal models on the role of histamine and its receptors in the eye, focusing on the effects of histamine H₃ receptor antagonists for the future treatment of glaucomatous patients. Full article

(This article belongs to the Special Issue New Developments in Histamine Research)

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16 pages, 9585 KiB

Open AccessReview

Histamine, Metabolic Remodelling and Angiogenesis: A Systems Level Approach

by Aurelio A. Moya-García, Almudena Pino-Ángeles, Francisca Sánchez-Jiménez, José Luis Urdiales and Miguel Ángel Medina

Biomolecules 2021, 11(3), 415; https://doi.org/10.3390/biom11030415 - 11 Mar 2021

Cited by 17 | Viewed by 6067

Abstract

Histamine is a highly pleiotropic biogenic amine involved in key physiological processes including neurotransmission, immune response, nutrition, and cell growth and differentiation. Its effects, sometimes contradictory, are mediated by at least four different G-protein coupled receptors, which expression and signalling pathways are tissue-specific. [...] Read more.

Histamine is a highly pleiotropic biogenic amine involved in key physiological processes including neurotransmission, immune response, nutrition, and cell growth and differentiation. Its effects, sometimes contradictory, are mediated by at least four different G-protein coupled receptors, which expression and signalling pathways are tissue-specific. Histamine metabolism conforms a very complex network that connect many metabolic processes important for homeostasis, including nitrogen and energy metabolism. This review brings together and analyses the current information on the relationships of the “histamine system” with other important metabolic modules in human physiology, aiming to bridge current information gaps. In this regard, the molecular characterization of the role of histamine in the modulation of angiogenesis-mediated processes, such as cancer, makes a promising research field for future biomedical advances. Full article

(This article belongs to the Special Issue New Developments in Histamine Research)

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26 pages, 1673 KiB

Open AccessReview

Histamine Intolerance: The Current State of the Art

by Oriol Comas-Basté, Sònia Sánchez-Pérez, Maria Teresa Veciana-Nogués, Mariluz Latorre-Moratalla and María del Carmen Vidal-Carou

Biomolecules 2020, 10(8), 1181; https://doi.org/10.3390/biom10081181 - 14 Aug 2020

Cited by 128 | Viewed by 46450

Abstract

Histamine intolerance, also referred to as enteral histaminosis or sensitivity to dietary histamine, is a disorder associated with an impaired ability to metabolize ingested histamine that was described at the beginning of the 21st century. Although interest in histamine intolerance has considerably grown [...] Read more.

Histamine intolerance, also referred to as enteral histaminosis or sensitivity to dietary histamine, is a disorder associated with an impaired ability to metabolize ingested histamine that was described at the beginning of the 21st century. Although interest in histamine intolerance has considerably grown in recent years, more scientific evidence is still required to help define, diagnose and clinically manage this condition. This article will provide an updated review on histamine intolerance, mainly focusing on its etiology and the existing diagnostic and treatment strategies. In this work, a glance on histamine intoxication will also be provided, as well as the analysis of some uncertainties historically associated to histamine intoxication outbreaks that may be better explained by the existence of interindividual susceptibility to ingested histamine. Full article

(This article belongs to the Special Issue New Developments in Histamine Research)

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