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Expression cloning of a cDNA encoding the bovine histamine H1 receptor.

ABSTRACT: A functional cDNA clone for the histamine H1 receptor was isolated from a cDNA library of bovine adrenal medulla by a combination of molecular cloning in an expression vector and electrophysiological assay in Xenopus oocytes. The H1 receptor cDNA encodes a protein of 491 amino acids (Mr 55,954) with seven putative transmembrane domains, illustrating the similarity to other receptors that couple with guanine nucleotide-binding regulatory proteins (G protein-coupled receptors). The sequence homology between the H1 and H2 receptors is not higher than that between the histamine H1 and m1-muscarinic receptors. The cloned receptor protein expressed in COS-7 cells bound specifically to [3H]mepyramine, an H1 receptor antagonist, and this binding was displaced by H1 receptor antagonists and histamine with affinities comparable with those in membranes of bovine adrenal medulla. H1 receptor mRNA was shown to be expressed in brain and in peripheral tissues, including lung, small intestine, and adrenal medulla. This investigation discloses the molecular nature of the H1 receptor--a receptor that mediates diverse neuronal and peripheral actions of histamine and that may be of therapeutic importance in allergy.

SUBMITTER: Yamashita M

PROVIDER: S-EPMC53166 | biostudies-other | 1991 Dec

REPOSITORIES: biostudies-other

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Expression cloning of a cDNA encoding the bovine histamine H1 receptor.

Yamashita M M Fukui H H Sugama K K Horio Y Y Ito S S Mizuguchi H H Wada H H

Proceedings of the National Academy of Sciences of the United States of America 19911201 24

A functional cDNA clone for the histamine H1 receptor was isolated from a cDNA library of bovine adrenal medulla by a combination of molecular cloning in an expression vector and electrophysiological assay in Xenopus oocytes. The H1 receptor cDNA encodes a protein of 491 amino acids (Mr 55,954) with seven putative transmembrane domains, illustrating the similarity to other receptors that couple with guanine nucleotide-binding regulatory proteins (G protein-coupled receptors). The sequence homolo ...[more]

PMID: 1722337

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Project description:Numerous host factors, in addition to human angiotensin-converting enzyme 2 (hACE2), have been identified as coreceptors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrating broad viral tropism and diversified druggable potential. We and others have found that antihistamine drugs, particularly histamine receptor H1 (HRH1) antagonists, potently inhibit SARS-CoV-2 infection. In this study, we provided compelling evidence that HRH1 acts as an alternative receptor for SARS-CoV-2 by directly binding to the viral spike protein. HRH1 also synergistically enhanced hACE2-dependent viral entry by interacting with hACE2. Antihistamine drugs effectively prevent viral infection by competitively binding to HRH1, thereby disrupting the interaction between the spike protein and its receptor. Multiple inhibition assays revealed that antihistamine drugs broadly inhibited the infection of various SARS-CoV-2 mutants with an average IC50 of 2.4 µM. The prophylactic function of these drugs was further confirmed by authentic SARS-CoV-2 infection assays and humanized mouse challenge experiments, demonstrating the therapeutic potential of antihistamine drugs for combating coronavirus disease 19.IMPORTANCEIn addition to human angiotensin-converting enzyme 2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can utilize alternative cofactors to facilitate viral entry. In this study, we discovered that histamine receptor H1 (HRH1) not only functions as an independent receptor for SARS-CoV-2 but also synergistically enhances ACE2-dependent viral entry by directly interacting with ACE2. Further studies have demonstrated that HRH1 facilitates the entry of SARS-CoV-2 by directly binding to the N-terminal domain of the spike protein. Conversely, antihistamine drugs, primarily HRH1 antagonists, can competitively bind to HRH1 and thereby prevent viral entry. These findings revealed that the administration of repurposable antihistamine drugs could be a therapeutic intervention to combat coronavirus disease 19.

Dataset Information

Expression cloning of a cDNA encoding the bovine histamine H1 receptor.

Publications

Expression cloning of a cDNA encoding the bovine histamine H1 receptor.

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