Role of histamine in the pathophysiology of asthma: immunomodulatory and anti-inflammatory activities of H1-receptor antagonists
Section snippets
Actions of histamine
During allergic reactions, both immunologic and nonimmunologic triggers stimulate release of histamine from cytoplasmic granules of mast cells and basophils. Depending on the location of these cells, histamine release causes such symptoms as acute rhinitis, bronchospasm, diarrhea, cramping, or cutaneous wheal and flare responses.1, 2 The majority of the acute symptoms in urticaria, allergic rhinitis, and allergic asthma are the result of the very rapid activity of histamine on vascular
Histamine mediators
Histamine triggers its effects by activating one of the histamine-type membrane receptors. The H1 receptor possesses all of the structural features of G-protein–coupled receptors, including 7 transmembrane domains, amino terminal glycosylation sites, and protein kinase A and protein kinase C phosphorylation sites.9 H1 receptors have been detected in the mammalian brain,10 airway smooth muscle,11, 12 gastrointestinal tract,13 genitourinary system,14 vascular smooth muscle,15 endothelial cells,5
Histamine implicated in pathophysiology of asthma
A number of findings point to a pathophysiologic role for histamine in asthma. Histamine has been detected in the airways of asthmatic persons, even during asymptomatic periods,22, 23, 24 and an increased number of degranulated mast cells and basophils have been detected in biopsies of asthmatic airways, even when the biopsies were obtained long after an acute asthma attack.25, 26 The level of histamine in bronchoalveolar lavage fluid (BALF) has been found to correlate with the severity of
Clinical trials of antihistamines in asthma
Because many of the effects of histamine on macrophages, dendritic cells, endothelial cells, and epithelial cells can be prevented by H1-receptor antagonists (Table 2),28, 29, 30, 31 there has been a resurgence of interest in the potential of these agents in the treatment of asthma. The potential efficacy of H1 antihistamines in asthma has been under investigation for >50 years.32 Inhalation of chlorpheniramine and clemastine was found to produce acute bronchodilation,33, 34 but these compounds
Identifying therapeutic targets
We have used a murine model of allergen-induced airway inflammation and methacholine-induced airway hyperresponsiveness to clarify mechanisms of airway function, to identify potential therapeutic targets, and to investigate the effects of the H1-receptor antagonist fexofenadine.64, 65, 66, 67, 68, 69, 70 In this model, the BALB/c strain of mice were sensitized to ovalbumin and then rechallenged with allergen 2 weeks later. Airway responsiveness to inhaled methacholine was assessed 2 days after
Conclusions
It would appear that if there is a role for second- or third-generation antihistamines in the treatment of asthma, patient selection and dosing are important considerations. Histamine may be a dominant pathophysiologic factor in patients with mild to moderately severe seasonal asthma, and the inflammation and symptoms that ensue may be susceptible to H1-receptor antagonist blockade. However, clinical trials as well as in vitro and laboratory investigations suggest that H1 antagonists may have
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Biomimetic solid-state nanochannels for chemical and biological sensing applications
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2018, European Journal of Pharmaceutical SciencesLabel-free histamine detection with nanofluidic diodes through metal ion displacement mechanism
2017, Colloids and Surfaces B: BiointerfacesCitation Excerpt :A disturbance in the level of neurotransmitter content can adversely affect the transmission process, leading to depression, schizophrenia, drug dependence and degenerative diseases in human beings [2]. Histamine (Hm) naturally occurs in human body in trace amounts and plays a key role in physiological functions controlled by brain, for example, neurotransmission, sleep, memory storage, thermoregulation, inflammation, secretion of hormones and gastric acid, food intake and cardiovascular control [3–6]. An excess of Hm level in the body can cause Alzheimer’s disease, abnormal arousal, asthma, allergies and some other neuropsychiatric disorders [7,8].
Potential effect of the extract of Zataria multiflora and its constituent, carvacrol, on lung pathology, total and differential WBC, IgE and eosinophil peroxidase levels in sensitized guinea pigs
2014, Journal of Functional FoodsCitation Excerpt :The extract of Z. multiflora and its constituent, carvacrol, also showed inhibitory effect on histamine (H1) receptor (Boskabady, Tabanfar, Gholamnezhad, & Sadeghnia, 2012b) which could be due to its anti-inflammatory effect and support the results of the present study. Previous studies also showed preventive effects of anti-inflammatory drugs on pathological changes (Bush, 2008; Durrani, Viswanathan, & Busse, 2011), total and differential WBC count (Boskabady, Eslamizade, Tabatabaei, Nemati, & Mansouri, 2010) and inflammatory mediators (Erwin & Gelfand, 2002) of sensitized animals and asthmatic patients, supporting the claim that the results seen for the extract and carvacrol are due to their anti-inflammatory effects. In addition, the results of the present study showed comparable effects of the extract and carvacrol with those of dexamethasone which is also an evidence indicating the anti-inflammatory effect of the plant and its constituent, carvacrol.