The role of histamine and its receptors in the pathogenesis of asthma

White, Janine P.; Eiser, Noemi M.

doi:10.1016/0007-0971(83)90046-3

Cited by 40 publications

(8 citation statements)

References 74 publications

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“…The clinical efficacy of Hpblockers in asthma is at best poor (53). We are not aware of any studies of the effect of long-term treatment of asthmatics with histamine Hj-antagonists.…”

Section: Locally Administered Histamine Induces Bron-mentioning

confidence: 98%

“…The Hj-philic leukocytes in vitro suggest that histamine blocker cimetidine has no effect or else it aug-may regulate its own release by a feedback rnents the response, but apparently only in inhibition via Hg-receptor stimulation (17,49). asthmatics (10,20,22,34,44,53).…”

Section: Locally Administered Histamine Induces Bron-mentioning

confidence: 99%

“…In accordance with this, cimetidine (an Hg-blocker) does not seem to augment antigen-induced bronchial reactions (19,44) or naturally occurring or exerciseinduced asthma (16); rather Eiser et al (10) reported inhibition of allergen-induced bronchospasms by intravenous cimetidine. Thus, the functional significance of Hg-receptors in human airways seems to be of minor importance in provocation tests of asthmatics with histamine or allergen (53).…”

Section: Locally Administered Histamine Induces Bron-mentioning

confidence: 99%

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Effects of Long‐Term Treatment with Low Dose Cimetidine on Allergen‐Induced Airway Responses and Selected Immunological Parameters in Atopic Asthmatics

Bergstrand

Hegardt²,

Löuwhagen

et al. 1985

Allergy

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Twenty asymptomatic atopic asthmatics were treated with either cimetidine 100 mg orally (13 patients) or placebo (7 patients) once a day for 4 weeks. Bronchial challenges were performed with the pertinent allergen immediately before and 2 and 4 weeks after the initiation of treatment and, finally, 4 weeks after the cessation of treatment. Before each challenge blood was drawn for the determination of specific IgE antibody levels (RAST procedure) and total IgE (PRIST), allergen- and anti-IgE-induced basophil histamine release, and mitogen-induced lymphocyte (3H)-thymidine incorporation. Patients treated with cimetidine were found to be significantly (P less than 0.05) less responsive to bronchial allergen challenge during the treatment than before it; patients treated with placebo were more reactive (P less than 0.05) 14 days after the initiation of treatment. The difference in responsiveness to treatment between the placebo and the cimetidine groups was significant 14 days (P less than 0.01) and 4 weeks (P less than 0.05) after the initiation of treatment; no significant difference in allergen responsiveness was recorded between the groups 1 month after cessation of treatment. No clear-cut changes in specific IgE antibody or total IgE levels, histamine release capacity, or mitogen-induced lymphocyte responsiveness were observed in either group, except that lymphocytes from cimetidine-treated patients tended to show an increased ratio of PHA- to PMA-induced thymidine incorporation. Thus, it was found that the treatment of asymptomatic atopic asthmatics with low-dose cimetidine reduced their allergen sensitivity in bronchial provocation tests by a mechanism which remains to be elucidated.

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“…The clinical efficacy of Hpblockers in asthma is at best poor (53). We are not aware of any studies of the effect of long-term treatment of asthmatics with histamine Hj-antagonists.…”

Section: Locally Administered Histamine Induces Bron-mentioning

confidence: 98%

Section: Locally Administered Histamine Induces Bron-mentioning

confidence: 99%

Section: Locally Administered Histamine Induces Bron-mentioning

confidence: 99%

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Effects of Long‐Term Treatment with Low Dose Cimetidine on Allergen‐Induced Airway Responses and Selected Immunological Parameters in Atopic Asthmatics

Bergstrand

Hegardt²,

Löuwhagen

et al. 1985

Allergy

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“…and as many of the earlier Hi-antihistamincs possessed alternative actions it is difficult to be specific as to which property of these agents is pertinent to the bronchodilatation. It has, however, been proposed that a variable histaminergic tone within the airways is responsible for the variable bronchodilatation [64]. Those patients with the most marked airflow obstruction exhibiting the greatest histaminergic tone are thus likely to respond best to Hiantihistamines [64].…”

Section: Bronchodilatationmentioning

confidence: 99%

Histamine and asthma: an appraisal based on specific H₁‐receptor antagonism

Howarth

1990

Clin Experimental Allergy

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H1-receptor antagonists have been utilized, following their initial chemical synthesis in 1933, both in the treatment of conditions in which histamine is considered to be of pathogenic importance and conversely to help elucidate the role of histamine in disease, through an evaluation of their influence on disease expression. While there is considerable indirect evidence to implicate histamine in the pathogenesis of asthma, a critical evaluation of H1-receptor antagonism in this condition has, until recently, proved difficult, as many of the early H1-receptor antagonists possessed additional actions, such as anti-cholinergic, local anaesthetic, alpha-adrenoceptor antagonistic and anti-serotonin activity. In addition, H1-receptor antagonists have been shown to have effects on mast cell function. In low concentrations in vitro, antihistamines have been found to inhibit immunologically stimulated mast cell mediator release, with the IC50 in the nanomolar to micromolar range, while at higher concentrations they induce histamine release. The potency of these drugs in producing such effects is unrelated to their H1-receptor blocking activity. Furthermore the sedative effects of these therapeutic agents limit the tolerable administrable dose and thus the degree of H1-receptor blockade achievable within the airways. The recent development of H1-receptor antagonists devoid of clinical sedative effects has enabled the administration of doses of H1-antihistamines which achieve a greater degree of H1-receptor blockade within the airways, thus permitting a better appraisal of the role of histamine in this condition. Furthermore, the receptor specificity of many of these agents has been focused such that terfenadine, astemizole, loratadine and cetirizine are devoid of anticholinergic activity and exhibit little alpha-antagonistic or anti-serotonin activity of clinical relevance. However, of these agents both loratadine and cetirizine possess additional actions likely to be of relevance to asthma. Pretreatment with loratadine has been shown to reduce the recovery of both histamine and prostaglandin D2 (PGD2) in nasal lavage fluid following nasal allergen challenge, a finding interpreted as indicative of in vivo mast cell stabilization, and cetirizine has been shown in vivo at therapeutic doses to inhibit allergen-induced eosinophil chemotaxis. Thus while both these agents offer the potential of an oral therapy for asthma based on an H1-receptor antagonist, their additional actions do not make them ideally suited to the exploration of the role of histamine in asthma.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…Of course, in airway diseases such as COPD and asthma enhanced airway luminal narrowing is caused by excessive shortening of ASM. The excessive shortening could result from exposure to spasmogens (Driver et al, 1993; Lam et al, 1988; Mattoli et al, 1991; Murray et al, 1986; Wenzel et al, 1991; White and Eiser, 1983), increased ASM mass (Hogg et al, 2004), increased myocyte contractility (Opazo Saez et al, 2000), reduced load on ASM (Bosse et al, 2007), or length adaptation of myocytes to passively or actively shortened lengths (McParland et al, 2005). However, another property of ASM which could affect nascent airway diameter is the force generation in the absence of concurrent neural or humeral (i.e.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of intrinsic force in small human airways

Wylam

Xue

Sieck

2012

Respiratory Physiology & Neurobiology

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We quantified the magnitude and investigated mechanisms regulating intrinsic force (IF) in human airway smooth muscle (hASM). IF was identified by reducing extracellular calcium (Ca2+) concentration to nominally zero in freshly isolated isometrically mounted 2 mm human bronchi. Our results show: (1) the magnitude of IF is ~ 50% of the maximal total force elicited by acetylcholine (10-5 M) and is epithelial-independent, (2) IF can also be revealed by β-adrenergic activation (isoproterenol), non-specific cationic channel blockade (La3+) or L-type voltage gated Ca2+ channel blockade (nifedipine), (3) atropine, indomethacin, AA– 861, or pyrilamine did not affect IF, (4) IF was reduced by the intracellular Ca2+ ([Ca2+]i) chelating agent BAPTA-AM, (5) ω-conotoxin had no effect on IF. In studies in cultured hASM cells nominally zero Ca2+ buffer and BAPTA-AM reduced [Ca2+]i but isoproterenol and nifedipine did not. Taken together these results indicate that rapid reduction of [Ca2+]i reveals a permissive relationship between extracellular Ca2+, [Ca2+]i and IF. However IF can be dissipated by mechanisms effecting Ca2+ sensitivity. We speculate that an increase of IF, a fundamental property of ASM, could be related to human airway clinical hyperresponsiveness and must be accounted for in in vitro studies of hASM.

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The role of histamine and its receptors in the pathogenesis of asthma

Cited by 40 publications

References 74 publications

Effects of Long‐Term Treatment with Low Dose Cimetidine on Allergen‐Induced Airway Responses and Selected Immunological Parameters in Atopic Asthmatics

Effects of Long‐Term Treatment with Low Dose Cimetidine on Allergen‐Induced Airway Responses and Selected Immunological Parameters in Atopic Asthmatics

Histamine and asthma: an appraisal based on specific H₁‐receptor antagonism

Mechanisms of intrinsic force in small human airways

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The role of histamine and its receptors in the pathogenesis of asthma

Cited by 40 publications

References 74 publications

Effects of Long‐Term Treatment with Low Dose Cimetidine on Allergen‐Induced Airway Responses and Selected Immunological Parameters in Atopic Asthmatics

Effects of Long‐Term Treatment with Low Dose Cimetidine on Allergen‐Induced Airway Responses and Selected Immunological Parameters in Atopic Asthmatics

Histamine and asthma: an appraisal based on specific H1‐receptor antagonism

Mechanisms of intrinsic force in small human airways

Contact Info

Product

Resources

About

Histamine and asthma: an appraisal based on specific H₁‐receptor antagonism