Effect of histamine H4 receptor antagonist on allergic rhinitis in mice

Takahashi, Yuji; Kagawa, Yoto; Izawa, Kana; Ono, Rie; Akagi, Masaaki; Kamei, Chiaki

doi:10.1016/j.intimp.2009.02.011

Cited by 53 publications

(36 citation statements)

References 33 publications

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“…JNJ7777120 has been used extensively to elucidate the roles of the H 4 receptor in a variety of allergic and inflammatory processes, including chemotaxis of eosinophils (Ling et al, 2004) and mast cells , as well as allergic rhinitis (Takahashi et al, 2009) and allergic airway inflammation (Dunford et al, 2006). Taken together, these data demonstrate that JNJ7777120 has anti-inflammatory properties and suggest that H 4 receptor antagonists may constitute a new class of anti-inflammatory drugs.…”

Section: Introductionmentioning

confidence: 82%

Agonist-Biased Signaling at the Histamine H₄ Receptor: JNJ7777120 Recruits β-Arrestin without Activating G Proteins

Rosethorne¹,

Charlton²

2010

Mol Pharmacol

102

132

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The G i/o -coupled histamine H 4 receptor is highly expressed in hemopoietic cells and is a promising new target for the treatment of chronic inflammatory diseases. 1-[(5-Chloro-1H-indol-2-yl)carbonyl]-4-methyl-piperazine (JNJ7777120) has been described as a selective antagonist at the H 4 receptor and is widely used to characterize the physiological role of the H 4 receptor. We have investigated the pharmacological properties of JNJ7777120 using two distinct downstream signaling measurements, G protein activation and ␤-arrestin recruitment. The H 4 receptor agonists histamine and clobenpropit, but not JNJ7777120, were able to induce [35 S]GTP␥S binding in membranes prepared from U2OS-H 4 cells. Thioperamide, a dual H 3 /H 4 receptor antagonist, and JNJ7777120 were both able to inhibit the [ 35 S]GTP␥S binding induced by clobenpropit. Agonists and antagonists specific for other members of the histamine receptor family had no effect in this assay format. Histamine and clobenpropit increased ␤-arrestin recruitment to the H 4 receptor in a concentration-dependent manner. This ␤-arrestin recruitment could be inhibited by preincubation with thioperamide. We were surprised to find that preincubation with the H 4 -selective antagonist JNJ7777120 potentiated rather than antagonized the response to a submaximal concentration of clobenpropit. JNJ7777120 treatment alone resulted in an increase in ␤-arrestin recruitment, which again could be inhibited by preincubation with thioperamide. Schild analysis demonstrated competitive antagonism between thioperamide and both clobenpropit and JNJ7777120. Histamine and clobenpropit had comparable potencies for both [ 35 S]GTP␥S binding and ␤-arrestin recruitment, suggesting little difference in the levels of receptor reserve between the two assays. In conclusion, we have demonstrated that JNJ7777120 recruits ␤-arrestin to the H 4 receptor, independent of G protein activation.

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Section: Introductionmentioning

confidence: 82%

Agonist-Biased Signaling at the Histamine H₄ Receptor: JNJ7777120 Recruits β-Arrestin without Activating G Proteins

Rosethorne¹,

Charlton²

2010

Mol Pharmacol

102

132

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“…18,19 Evidence for H 4 receptor involvement in conjunctivitis and rhinitis has been reported in mouse models of these allergic conditions. 25,32 In both of these reports, the H 4 receptor antagonist, JNJ7777120, significantly reduced allergic symptoms, and the effect could be ascribed to blockade of H 4 receptors. Combined treatment with JNJ7777120 and the H 1 antagonist levocabastine reduced signs and symptoms of allergic conjunctivitis to a greater extent than either agent alone.…”

Section: Notesmentioning

confidence: 93%

Alcaftadine, a new antihistamine with combined antagonist activity at histamine H1, H2, and H4 receptors

Gallois-Bernos¹,

Thurmond²

2012

JRLCR

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Current therapy for ocular allergy includes H 1 antihistamines, mast cell stabilizers, dual action antihistamines (H 1 antihistamines + mast cell stabilizers), and steroids. In this report, we describe the in vivo and in vitro characterization of alcaftadine, a recently approved antihistamine that exhibits a distinct set of therapeutic properties. When tested in a guinea pig model of conjunctivitis, alcaftadine prevented immediate allergic responses with an efficacy comparable with that of ketotifen, and was also able to attenuate delayed eosinophil influx with a potency similar to that of dexamethasone. Given recent reports suggesting a possible role for histamine H 2 or H 4 receptors in the etiology of ocular allergy, we examined the binding properties of alcaftadine at all histamine receptor types. Alcaftadine is a high affinity ligand for the H 1 receptor, with a pK i (8.5) that is comparable with that of other H 1 antihistamines. It also shows an higher affinity for the H 2 receptor than ketotifen. Alcaftadine exhibited modest binding affinity for the H 4 receptor (pK i = 5.8) with no affinity for the H 3 receptor. The affinity for the H 4 is higher than the value for ketotifen (pK i , 5). Using a cellular assay of H 4 receptor activity, alcaftadine was shown to act as a functional antagonist of H 4 receptor signaling. Overall, the studies suggest that alcaftadine is a histamine receptor antagonist with a broad spectrum of antihistamine activity and a unique combination of therapeutic effects. As such, it represents a new therapeutic option for the treatment of allergic conditions.

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“…Furthermore, it caused a significant decrease in the levels of IL-4 and a significant increase in the levels of IFN-in nasal lavage fluid. These results indicated that histamine H 4 receptor was closely related with allergic rhinitis and was important in the pathogenesis of allergic rhinitis [59,107]. Scientists at Palau Pharma, A Biopharmaceutical company, developed series of furo-[3, 2-d]-pyrimidine derivatives as H 4 receptor antagonists.…”

Section: H 4 Receptor Ligands: Potential Modulators Of Allergic and Imentioning

confidence: 96%

Histamine H4 Receptor: A Novel Therapeutic Target for Immune and Allergic Responses

Bhatt

Agrawal²,

Raval³

et al. 2010

MRMC

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HIstamine is a biomolecular compound located in various parts of body. It participated in various important cellular activities associated with allergy and asthma. This magic bio-molecule is directly and indirectly involved in various biochemical reactions through G-protein couple receptors. Various histamine receptors and their unexplored biochemical activities attracted many biologists in last few decades. A surprising discovery of histamine H(4) receptor was done when scientist worked on histamine H(3) receptor in brain cells. The binding pocket of histamine H(4) differs by transmembrane domains (TM3, TM5 and TM6) from histamine H(3)-sub type. In this review, we enlightened various functions of histamine H(4) and use of histamine H(4) receptor antagonists in autoimmune diseases, allergic responses, inflammatory responses, and in superoxide generation which are helpful to establish H(4) receptor antagonists as newer anti histamines.

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Effect of histamine H4 receptor antagonist on allergic rhinitis in mice

Cited by 53 publications

References 33 publications

Agonist-Biased Signaling at the Histamine H₄ Receptor: JNJ7777120 Recruits β-Arrestin without Activating G Proteins

Agonist-Biased Signaling at the Histamine H₄ Receptor: JNJ7777120 Recruits β-Arrestin without Activating G Proteins

Alcaftadine, a new antihistamine with combined antagonist activity at histamine H1, H2, and H4 receptors

Histamine H4 Receptor: A Novel Therapeutic Target for Immune and Allergic Responses

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Effect of histamine H4 receptor antagonist on allergic rhinitis in mice

Cited by 53 publications

References 33 publications

Agonist-Biased Signaling at the Histamine H4 Receptor: JNJ7777120 Recruits β-Arrestin without Activating G Proteins

Agonist-Biased Signaling at the Histamine H4 Receptor: JNJ7777120 Recruits β-Arrestin without Activating G Proteins

Alcaftadine, a new antihistamine with combined antagonist activity at histamine H1, H2, and H4 receptors

Histamine H4 Receptor: A Novel Therapeutic Target for Immune and Allergic Responses

Contact Info

Product

Resources

About

Agonist-Biased Signaling at the Histamine H₄ Receptor: JNJ7777120 Recruits β-Arrestin without Activating G Proteins

Agonist-Biased Signaling at the Histamine H₄ Receptor: JNJ7777120 Recruits β-Arrestin without Activating G Proteins