Role of the Histamine H4-Receptor in Bronchial Asthma

Abstract

Histamine is a pro-inflammatory mediator with a prominent role in allergic diseases. Antagonists at the histamine receptor subtype 1 are central in anti-allergic therapies, with the exception of allergic asthma, where they are clinically without effect. The latest identified histamine receptor subtype 4, which is expressed mainly in hematopoietic cells, now provides a reasonable target for new therapeutic strategies inhibiting histamine function. The pathophysiology of allergy, esp. allergic asthma, and in its context the effects of antagonists at the histamine receptor subtype 4 in preclinical and clinical settings are discussed in this chapter.

Application of Metabolomics in Pediatric Asthma: Prediction, Diagnosis and Personalized Treatment

“…This might be explained by the H4 receptor that is expressed by inflammatory cells. Low histamine levels appear to induce recruitment of dendritic cells, eosinophils and mast cells facilitated by the H4 receptors [ 87 ]. Therefore, low concentrations of urinary methyl-imidazole acetic acid in atopic asthma would be a marker of alterations in histamine metabolism.…”

UR-DEBa242: A Py-5-Labeled Fluorescent Multipurpose Probe for Investigations on the Histamine H3 and H4 Receptors

“…Based on its expression profile and experimental evidence, the H 4 R is suggested to play a (patho)physiological role in autoimmune and allergic disorders (e.g. pruritus 198,199 , atopic dermatitis 200 , bronchial asthma 201 , ulcerative colitis 202 and rheumatoid arthritis 203 ) and in cancer 204,205 . As a consequence of the above-mentioned low sequence homology between the human H 4 R and its rodent orthologs, high constitutive activity was predominantly observed for the human H 4 R in recombinant and overexpressing systems.…”

“…b Data taken from Mocking et al, determined by BRET-based competition binding experiments with clobenpropit-BODIPY-630/650 at the NLuc-hH 3 R or NLuc-hH 4 R, transiently expressed in intact HEK293T cells. 20 c Data from radioligand competition binding experiments with [1] [ 3 H]2, [2−6] [ 3 H]1, [7] [ 3 H]6, or [8,9] [ 3 H]-N α -methylhistamine performed on[1] membrane preparations of Sf 9 insect cells, stably expressing the hH 3 R + Gα i2 + Gβ 1 γ 2 + RGS4 or the hH 4 R-RGS19 fusion protein + Gα i2 + Gβ 1 γ 2 ,12 [2] membrane preparations of Sf 9 insect cells, stably expressing the hH 4 R-RGS19 fusion protein + Gα i2 + Gβ 1 γ 2 ,10 [3] membrane preparations of Sf 9 insect cells, stably expressing the hH 4 R + Gα i2 + Gβ 1 γ 2 ,…”

The Novel H4R Antagonist 1-[(5-Chloro-2,3-Dihydro-1-Benzofuran-2-Yl)Methyl]-4-Methyl-Piperazine (LINS01007) Attenuates Several Symptoms in Murine Allergic Asthma

“…The histamine H 4 R is coupled to G i/o protein and thus leads to reduction of intracellular AMPc and calcium levels, but its G-protein independent signaling pathway was also reported [6]. It is expressed in bone marrow derived and immune cells such as eosinophils, neutrophils, basophils, T lymphocytes, mast and dendritic cells, thus actively participating on inflammatory response [6].…”