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Graziella Vecchio - One of the best experts on this subject based on the ideXlab platform.

Manzoor M Khan - One of the best experts on this subject based on the ideXlab platform.

  • effects of lymphokines and mitogens on a Histamine Derivative induced intracellular calcium mobilization and inositol phosphate production
    1994
    Co-Authors: Kenneth L Melmon, Manzoor M Khan
    Abstract:

    Histamine trifluoromethyl-toluidide Derivative (HTMT), a novel imrnunosuppressive agent, stimulates H1, H2 and HTMT receptors in lymphocytes. HTMT receptors are different from the classical H2, H2 or H3 receptors. Stimulation of HTMT receptors results in increased intracellular concentrations of calcium ([Ca2+]i) and inositol phosphate (IP) in human peripheral blood lymphocytes. In the present study, we investigated the effects of lymphokines [interleukin-4 (IL-4), interleukin-2 (IL-2)] and other pharmacologic agents [lipopolysaccharide (LPS), phorbol 12-myristate 13-acetate (PMA)] on HTMT-induced Ca2+ and IP responses in non-rosetted cells. HTMT caused enhanced [Ca2+]i and IP responses when the cells were pretreated with IL-4. The effects of IL-4 were concentration dependent and became maximal after the cells were incubated with IL-4 for 48 hr. Inhibitors of protein synthesis, but not of RNA synthesis, blocked the effects of IL-4 on HTMT-induced responses. LPS was more potent than IL-4 in augmenting Ca2+ mobilization induced by HTMT. However, the effects of LPS were not altered by inhibitors of either protein synthesis or RNA transcription. This indicated that LPS may act differently than IL-4 on the HTMT response. IL-2 and PMA did not affect HTMT-induced [Ca2+]i and IP responses. The effects of IL-4 and LPS were agonist specific. They did not affect the Ca2+ mobilization induced by PAF. The data indicate that the response to HTMT can be regulated by IL-4 and LPS. Although the in vivo importance of these receptors is not yet clear, the receptor is likely a contributor to immune and/or inflammatory regulation.

  • a Histamine Derivative increases intracellular calcium mobilization and oxidative metabolism in hl 60 cells
    1993
    Co-Authors: Rong Qiu, Kenneth L Melmon, Manzoor M Khan
    Abstract:

    Abstract Past work in our laboratory has shown that a Derivative of Histamine, Histamine-trifluoromethyl-toluidide (HTMT), has surprising tissue specificity on lymphocytes and can produce remarkable immunosuppression. This study focuses on the effects of HTMT on Ca2+ mobilization and oxidative metabolism in undifferentiated and DMSO-differentiated HL-60 cells. HTMT caused two phases of increases in intracellular calcium concentrations ([Ca2+]i) in HL-60 cells. The responses were dose dependent, with similar EC50 values (1.7×10−5M for undifferentiated and 1.5×10−5M for differentiated cells). The increase in [Ca2+]i in differentiated cells was much greater than in undifferentiated cells. The maximum responses were observed after the undifferentiated cells were incubated with DMSO for 7 days. The increase in [Ca2+]i induced by HTMT in both types of cells was competitively antagonized by high concentrations of Histamine but not by classic Histamine receptor antagonists (H1, H2, or H3). The inhibitory effects of Histamine on [Ca2+]i accumulation in differentiated cells were partially reversed by Histamine H2 receptor antagonist ranitidine, whereas in undifferentiated cells, the effects of Histamine on Ca2+ mobilization were not affected by ranitidine. Other cAMP elevating agents did not inhibit increases in [Ca2+]i in undifferentiated cells but did effect [Ca2+]i in differentiated cells. The enhanced response in [Ca2+]i mobilization after differentiation of HL-60 cells appeared to be the result of an increase in the expression/function of receptors for HTMT. One interesting feature of this regulation was the fact that cAMP per se did not regulate HTMT induced Ca2+ mobilization in undifferentiated cells but inhibited the mobilization in differentiated cells. HTMT caused the generation of reactive oxygen species in both undiffrentiated and differentiated HL-60 cells as measured by chemoluminescence and the levels of generation correlated with the mobilization of [Ca2+]i. In addition, the EC50s for the HTMT induced calcium mobilization and the generation of reactive oxygen species were similar, as was the case for Histamine induced inhibition (Ki) in both cell types. The data imply a second messenger role for Ca2+ in HTMT induced neutrophil activation.

Vincenzo Cucinotta - One of the best experts on this subject based on the ideXlab platform.

Kenneth L Melmon - One of the best experts on this subject based on the ideXlab platform.

  • effects of lymphokines and mitogens on a Histamine Derivative induced intracellular calcium mobilization and inositol phosphate production
    1994
    Co-Authors: Kenneth L Melmon, Manzoor M Khan
    Abstract:

    Histamine trifluoromethyl-toluidide Derivative (HTMT), a novel imrnunosuppressive agent, stimulates H1, H2 and HTMT receptors in lymphocytes. HTMT receptors are different from the classical H2, H2 or H3 receptors. Stimulation of HTMT receptors results in increased intracellular concentrations of calcium ([Ca2+]i) and inositol phosphate (IP) in human peripheral blood lymphocytes. In the present study, we investigated the effects of lymphokines [interleukin-4 (IL-4), interleukin-2 (IL-2)] and other pharmacologic agents [lipopolysaccharide (LPS), phorbol 12-myristate 13-acetate (PMA)] on HTMT-induced Ca2+ and IP responses in non-rosetted cells. HTMT caused enhanced [Ca2+]i and IP responses when the cells were pretreated with IL-4. The effects of IL-4 were concentration dependent and became maximal after the cells were incubated with IL-4 for 48 hr. Inhibitors of protein synthesis, but not of RNA synthesis, blocked the effects of IL-4 on HTMT-induced responses. LPS was more potent than IL-4 in augmenting Ca2+ mobilization induced by HTMT. However, the effects of LPS were not altered by inhibitors of either protein synthesis or RNA transcription. This indicated that LPS may act differently than IL-4 on the HTMT response. IL-2 and PMA did not affect HTMT-induced [Ca2+]i and IP responses. The effects of IL-4 and LPS were agonist specific. They did not affect the Ca2+ mobilization induced by PAF. The data indicate that the response to HTMT can be regulated by IL-4 and LPS. Although the in vivo importance of these receptors is not yet clear, the receptor is likely a contributor to immune and/or inflammatory regulation.

  • a Histamine Derivative increases intracellular calcium mobilization and oxidative metabolism in hl 60 cells
    1993
    Co-Authors: Rong Qiu, Kenneth L Melmon, Manzoor M Khan
    Abstract:

    Abstract Past work in our laboratory has shown that a Derivative of Histamine, Histamine-trifluoromethyl-toluidide (HTMT), has surprising tissue specificity on lymphocytes and can produce remarkable immunosuppression. This study focuses on the effects of HTMT on Ca2+ mobilization and oxidative metabolism in undifferentiated and DMSO-differentiated HL-60 cells. HTMT caused two phases of increases in intracellular calcium concentrations ([Ca2+]i) in HL-60 cells. The responses were dose dependent, with similar EC50 values (1.7×10−5M for undifferentiated and 1.5×10−5M for differentiated cells). The increase in [Ca2+]i in differentiated cells was much greater than in undifferentiated cells. The maximum responses were observed after the undifferentiated cells were incubated with DMSO for 7 days. The increase in [Ca2+]i induced by HTMT in both types of cells was competitively antagonized by high concentrations of Histamine but not by classic Histamine receptor antagonists (H1, H2, or H3). The inhibitory effects of Histamine on [Ca2+]i accumulation in differentiated cells were partially reversed by Histamine H2 receptor antagonist ranitidine, whereas in undifferentiated cells, the effects of Histamine on Ca2+ mobilization were not affected by ranitidine. Other cAMP elevating agents did not inhibit increases in [Ca2+]i in undifferentiated cells but did effect [Ca2+]i in differentiated cells. The enhanced response in [Ca2+]i mobilization after differentiation of HL-60 cells appeared to be the result of an increase in the expression/function of receptors for HTMT. One interesting feature of this regulation was the fact that cAMP per se did not regulate HTMT induced Ca2+ mobilization in undifferentiated cells but inhibited the mobilization in differentiated cells. HTMT caused the generation of reactive oxygen species in both undiffrentiated and differentiated HL-60 cells as measured by chemoluminescence and the levels of generation correlated with the mobilization of [Ca2+]i. In addition, the EC50s for the HTMT induced calcium mobilization and the generation of reactive oxygen species were similar, as was the case for Histamine induced inhibition (Ki) in both cell types. The data imply a second messenger role for Ca2+ in HTMT induced neutrophil activation.

Thierry Roisnel - One of the best experts on this subject based on the ideXlab platform.

  • Crystal structure of 2-(1H-imidazol-4-yl)ethanaminium chloride
    2015
    Co-Authors: Imene Belfilali, Siham Yebdri, Samira Louhibi, Leila Boukli-hacene, Thierry Roisnel
    Abstract:

    The title molecular salt, C5H10N3+·Cl−, was obtained as by-product in the attempted synthesis of a Histamine Derivative. The terminal amino group of the starting material is protonated. The Cimidazole—C—C—N(H3)+ group in the cation is in an anti conformation with a torsion angle of 176.22 (10)°. In the crystal, cations and anions are linked via N—H...N and N—H—Cl hydrogen bonds, forming a two-dimensional network parallel to (10-1). A single weak C—H...Cl hydrogen bond completes a three-dimensional network