Elsevier

Biochemical Pharmacology

Volume 40, Issue 8, 15 October 1990, Pages 1677-1681
Biochemical Pharmacology

Commentary
Histamine as an intracellular messenger

https://doi.org/10.1016/0006-2952(90)90341-HGet rights and content

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  • Cited by (77)

    • Histamine H3 and H4 receptors modulate Parkinson's disease induced brain pathology. Neuroprotective effects of nanowired BF-2649 and clobenpropit with anti-histamine-antibody therapy

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      Later, Panula, Steinbusch and others from 1988 to 1998 showed extensive details of histaminergic neurons and its projections throughout the rat brain and spinal cord and in human brain (Smits et al., 1990; Steinbusch 1991; Steinbusch et al., 1986; Wouterlood et al., 1986, 1987, 1988). These immunocytochemical mapping of histaminergic neurons established its role as a neurotransmitter in the central nervous system (CNS) (Brandes et al., 1990; Haas et al., 2008; Schwartz et al., 1980). With recent advancements in drugs targeting histamine receptors for various diseases, four metabotropic receptor types are identified as histamine H1, H2, H3 and H4 (Chazot, 2013; Panula et al., 2015; Roeder, 2003; Tiligada and Ennis, 2020).

    • The tumor-suppressor cholesterol metabolite, dendrogenin A, is a new class of LXR modulator activating lethal autophagy in cancers

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      The facts that:1) 5,6α-EC was the only isomer to react, 2) 5,6α-EC gave a single product of condensation with nucleophiles, and 3) the reaction needed a catalyst to occur, suggested a metabolic transformation pathway of 5,6-EC [3]. Because histamine was known as a ligand of the AEBS/ChEH complex [47,48], it was postulated that biogenic amines such as histamine or polyamines (spermine, spermidine or putrescine) could produce compounds with potent cancer cell differentiation properties at low concentrations. A series of conjugation products were synthesized and screened for their capacities to induce cell differentiation.

    • Improving the efficacy of hormone therapy in breast cancer: The role of cholesterol metabolism in SERM-mediated autophagy, cell differentiation and death

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      5,6α-EC was also shown to be a ligand for LXRα and a modulator for both the LXRα and β subtypes [78], however they have not been tested on other off-targets of Tam or other known oxysterol targets such as AhR [79,80], ROR [81–83], EBI2 [84], Hedgehog component smoothened [85], oxysterol-binding protein-related proteins [86] or ER [87,88]. Histamine (Fig. 1I) was shown to be an endogenous AEBS ligand [89–91], and recently a stereoselective conjugation product of the condensation of histamine and 5,6α-epoxycholesterol, named dendrogenin A (Fig. 1J), was identified and found to be an AEBS ligand [92–97]. Analysis of the structure of the known AEBS ligands suggested some links between AEBS and cholesterol metabolism.

    • From tamoxifen to dendrogenin A: The discovery of a mammalian tumor suppressor and cholesterol metabolite

      2016, Biochimie
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      Elimination of the phenylpropene part from the triphenylethylene backbone of Tam gives compounds such as tesmilifene (also known as DPPE) and PBPE, which have no ER affinity but retain a high affinity for the AEBS (Fig. 1) [12–18]. In the eighties, Brandes' group hypothesized that, since tesmilifene is a geometric isomer of the antihistaminic drugs phenyltoloxamine and diphenhydramine, the AEBS could be related to the histamine (HA) receptor, and provided the first evidence that HA is an AEBS ligand [19]. Tesmilifene and PBPE (Fig. 2) have also been successfully used to decipher the pharmacological role of the AEBS in the anticancer actions of Tam.

    • The CML-related oncoprotein BCR/ABL induces expression of histidine decarboxylase (HDC) and the synthesis of histamine in leukemic cells

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      These data suggest that the BCR/ABL-induced production of histamine in leukemic cells is mediated through a PI3-kinase-dependent signaling pathway. Several studies suggest that histamine promotes growth of hematopoietic progenitors through autocrine mechanisms involving transmembrane or intracellular histamine receptors.24-27,51,52 We therefore examined expression of histamine-binding sites in KU812 cells and K562 cells as well as in primary CML cells and normal BMMCs.

    • The role of histamine in the intracellular survival of Mycobacterium bovis BCG

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      The H1, H2 and H4 receptors are displayed on various immunocompetent cells, while the H3 receptor has been identified in the nervous system [46]. Furthermore, histamine has recently been shown to bind to an intracellular histamine receptor (the Hic receptor) containing cytochromes P450 and c, which is located in the microsomes and nucleus [47–49]. Histamine serves as one of the principal mediators of inflammation and allergic responses.

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