Abstract
Transient expression of the wild-type human histamine H(1) receptor in SV40-immortalised African green monkey kidney cells resulted in an agonist-independent elevation of the basal levels of the second messenger inositoltrisphospate. Several histamine H(1) receptor antagonists, including the therapeutically used anti-allergics cetirizine, loratadine and epinastine reduced this constitutive histamine H(1) receptor activity. Inverse agonism, i.e., stabilisation of an inactive conformation of the human histamine H(1) receptor, may therefore be a key component of the anti-allergic mechanism of action of clinically used antihistamines.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding, Competitive
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COS Cells
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Cell Line, Transformed
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Histamine / pharmacology
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Histamine Agonists / metabolism
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Histamine Agonists / pharmacology*
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Histamine H1 Antagonists / metabolism
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Histamine H1 Antagonists / pharmacology*
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Humans
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Inositol Phosphates / metabolism
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Methylhistidines / pharmacology
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Pyrilamine / metabolism
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Pyrilamine / pharmacology
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Radioligand Assay
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Receptors, Histamine H1 / drug effects*
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Receptors, Histamine H1 / genetics
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Receptors, Histamine H1 / metabolism
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Recombinant Fusion Proteins / drug effects
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
Substances
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Histamine Agonists
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Histamine H1 Antagonists
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Inositol Phosphates
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Methylhistidines
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Receptors, Histamine H1
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Recombinant Fusion Proteins
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alpha-fluoromethylhistidine
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Histamine
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Pyrilamine