Effect of ketanserin, a new blocking agent of the 5‐HT<sub>2</sub> receptor, on airway responsiveness in asthma

Cazzola, Mario; Assogna, G; Lucchetti, G; Cicchitto, Gaetano; D’Amato, Gennaro

doi:10.1111/j.1398-9995.1990.tb00473.x

Cited by 20 publications

(10 citation statements)

References 5 publications

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“…Since ketanserin competitively antagonized the 5-HT-induced contraction with a pK B value 9.15 in accordance with 9.4 in mouse aorta [25], we could demonstrate that the contraction was mediated via 5-HT 2A receptors. In analogy with a contractile role for 5-HT 2A receptors in the airway, ketanserin, has been demonstrated to decrease ovalbumin-induced airway hyperresponsiveness in mouse [26] and to be beneficial in asthmatic subjects [27]. …”

Section: Discussionmentioning

confidence: 99%

IL-1β induces murine airway 5-HT2A receptor hyperresponsiveness via a non-transcriptional MAPK-dependent mechanism

2007

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Background: Interleukin 1 beta (IL-1β) is found in bronchoalveolar lavage fluids from asthmatic patients and plays an important role in normal immunoregulatory processes but also in pathophysiological inflammatory responses. The present study was designed to investigate if IL-1β could be involved in the development of airway hyperresponsiveness and if transcriptional mechanisms, epithelium contractile factors and mitogen-activated protein kinase (MAPK) pathways are involved in IL-1β effect.

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Section: Discussionmentioning

confidence: 99%

IL-1β induces murine airway 5-HT2A receptor hyperresponsiveness via a non-transcriptional MAPK-dependent mechanism

2007

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“…However, the mechanism by which the effects of 5-HT were mediated is difficult to interpret in these studies as ketanserin, the 5-HT2 antagonist used in the study, also antagonizes the CCR3 receptor. Additionally, another study investigating bronchospasm in asthmatic humans showed that ketanserin had a protective effect on adenosine-induced bronchoconstriction (21). However, the mechanism by which ketanserin elicited these protective effects was not determined.…”

Section: Discussionmentioning

confidence: 99%

Cutting Edge: Serotonin Is a Chemotactic Factor for Eosinophils and Functions Additively with Eotaxin

Boehme

Lio

Sikora

et al. 2004

The Journal of Immunology

101

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Elevated levels of serotonin (5-hydroxytryptamine, 5-HT) are observed in the serum of asthmatics. Herein, we demonstrate that 5-HT functions independently as an eosinophil chemoattractant that acts additively with eotaxin. 5-HT2A receptor antagonists (including MDL-100907 and cyproheptadine (CYP)) were found to inhibit 5-HT-induced, but not eotaxin-induced migration. Intravital microscopy studies revealed that eosinophils roll in response to 5-HT in venules under conditions of physiological shear stress, which could be blocked by pretreating eosinophils with CYP. OVA-induced pulmonary eosinophilia in wild-type mice was significantly inhibited using CYP alone and maximally in combination with a CCR3 receptor antagonist. Interestingly, OVA-induced pulmonary eosinophilia in eotaxin-knockout (Eot−/−) mice was inhibited by treatment with the 5-HT2A but not CCR3 receptor antagonist. These results suggest that 5-HT is a potent eosinophil-active chemoattractant that can function additively with eotaxin and a dual CCR3/5-HT2A receptor antagonist may be more effective in blocking allergen-induced eosinophil recruitment.

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“…Doses used were adapted from other studies in which mice were treated with these receptor antagonists (Oishi et al , 1993; Garssen et al , 1993; Shaoheng & Walls, 1997) or according to the manufacturer's advice. Furthermore, animals were injected with a combination of cimetidine (10 mg kg −1 ) and ketanserin (12 mg kg −1 ) or with an α‐adrenoceptor antagonist (phentolamine, 5 mg kg −1 ) since ketanserin also has effects on these receptors (Cazzola et al , 1990). Control mice were injected with 0.25 ml sterile saline.…”

Section: Methodsmentioning

confidence: 99%

Modulation of airway hyperresponsiveness and eosinophilia by selective histamine and 5‐HT receptor antagonists in a mouse model of allergic asthma

Bie

Henricks

Cruikshank

et al. 1998

British J Pharmacology

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1 Since both histamine and 5-hydroxytryptamine (5-HT) can be released by murine mast cells, we investigated the possible role of these autacoids on airway hyperresponsiveness (AHR), eosinophil in®ltration and serum-IgE levels in a murine model of allergic asthma. 2 Ovalbumin-sensitized mice were exposed to either ovalbumin (2 mg ml 71 ) or saline aerosols on 8 consecutive days. Starting one day before the challenge, animals were injected i.p. twice a day with a 5-HT-type 1 (5-HT 1 ) or type 2 (5-HT 2 ) receptor antagonist (methiotepine, 1.25 or 2.0 mg kg 71 and ketanserin, 12 mg kg 71 , respectively) or a histamine-type 1 (H 1 ) or type 2 (H 2 ) receptor antagonist (mepyramine, 12 or 20 mg kg 71 and cimetidine, 10 or 25 mg kg 71 , respectively). Furthermore, animals were injected with a combination of cimetidine and ketanserin or with an a-adrenoceptor antagonist (phentolamine, 5 mg kg 71 ). 3 In vehicle-treated ovalbumin-challenged animals airway responsiveness to intravenous injections of methacholine in vivo was signi®cantly (9 fold increase, P50.01) increased when compared to vehicletreated saline-challenged animals. Furthermore, ovalbumin challenge of vehicle-treated animals induced a signi®cant increase in both eosinophil numbers in bronchoalveolar lavage (BAL)¯uid (0+0, vehicle/ saline and 15.0+5.9610 4 cells vehicle/ovalbumin, P50.05) and ovalbumin-speci®c IgE levels in serum (157+69 and 617+171 units ml 71, respectively, P50.05) compared to saline-challenged mice. Virtually no eosinophils could be detected in saline-challenged animals after all dierent treatments. 4 Treatment with ketanserin or cimetidine resulted in a partial but signi®cant decrease of the ovalbumin-induced AHR compared to ovalbumin-challenged controls (P50.05) and reduced eosinophil in®ltration after ovalbumin challenge by 60% and 58%, respectively. The combination of cimetidine and ketanserin almost completely abolished AHR whereas eosinophilia was decreased by 49%. No eects of these antagonists were observed on IL-16 levels in BAL¯uid or on serum antigen-speci®c IgE levels. Treatment with either the H 1 -receptor, the 5-HT 1 -receptor or the a-adrenoceptor antagonist, did not decrease the observed ovalbumin-induced airway responsiveness or eosinophilia in vehicle-treated animals. Higher doses of either methiotepine (2.0 mg kg 71 ) or mepyramine (20 mg kg 71 ) did decrease ovalbumin-induced eosinophil in®ltration (by 67%, P50.05 and 73%, respectively), whereas no eects of these antagonists were observed on ovalbumin-speci®c IgE levels in serum. 5 From these data it can be concluded that both histamine and 5-HT play a role in antigen-induced AHR and eosinophilia in the mouse.

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Effect of ketanserin, a new blocking agent of the 5‐HT₂ receptor, on airway responsiveness in asthma

Cited by 20 publications

References 5 publications

IL-1β induces murine airway 5-HT2A receptor hyperresponsiveness via a non-transcriptional MAPK-dependent mechanism

IL-1β induces murine airway 5-HT2A receptor hyperresponsiveness via a non-transcriptional MAPK-dependent mechanism

Cutting Edge: Serotonin Is a Chemotactic Factor for Eosinophils and Functions Additively with Eotaxin

Modulation of airway hyperresponsiveness and eosinophilia by selective histamine and 5‐HT receptor antagonists in a mouse model of allergic asthma

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Effect of ketanserin, a new blocking agent of the 5‐HT2 receptor, on airway responsiveness in asthma

Cited by 20 publications

References 5 publications

IL-1β induces murine airway 5-HT2A receptor hyperresponsiveness via a non-transcriptional MAPK-dependent mechanism

IL-1β induces murine airway 5-HT2A receptor hyperresponsiveness via a non-transcriptional MAPK-dependent mechanism

Cutting Edge: Serotonin Is a Chemotactic Factor for Eosinophils and Functions Additively with Eotaxin

Modulation of airway hyperresponsiveness and eosinophilia by selective histamine and 5‐HT receptor antagonists in a mouse model of allergic asthma

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Effect of ketanserin, a new blocking agent of the 5‐HT₂ receptor, on airway responsiveness in asthma