Biotinylated Heptapeptides with D-amino Acids Suppress Allergic Reactions by Inhibiting Mast Cell Activation and Antagonizing the Histamine Receptor

Makoto Ohira; Akiharu Uwamizu; Keita Hori; Yumi Obinata; Daisuke Uta; Junken Aoki; Keiichi Ebina; Tsukasa Matsumoto; Akira Sato

doi:10.1007/s10989-024-10670-2

Biotinylated Heptapeptides with D-amino Acids Suppress Allergic Reactions by Inhibiting Mast Cell Activation and Antagonizing the Histamine Receptor

Makoto Ohira, Akiharu Uwamizu, Keita Hori, Yumi Obinata, Daisuke Uta, Junken Aoki, Keiichi Ebina, Tsukasa Matsumoto, Akira Sato^*

^*Corresponding author for this work

Applied Pharmacology

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Mast cells play an important role in allergic reactions by releasing potent mediators, including histamine and platelet-activating factor (PAF), upon activation. We recently reported that a biotinylated heptapeptide (peptide 2), D-Lys(Biotinyl)-Trp-Tyr-Lys-Asp-Gly-Asp, which is highly stable in the plasma, inhibits PAF bioactivity and anaphylactic hypothermia in vivo. However, the effects of this peptide on allergy induction by mast cells have not been investigated. Methods and Results: Several biotinylated heptapeptides, including peptide 2, inhibited IgE/antigen-stimulated degranulation in RBL-2H3 cells. Peptide 2 also markedly inhibited the degranulation induced by calcium ionophore A23187. All peptides (peptide 1, 2 and 3) inhibited activating stimuli-induced increase in intracellular Ca²⁺ levels. The transforming growth factor-alpha shedding assay indicated that peptide 2 antagonized against the histamine H₁ receptor. Furthermore, peptide 2 inhibited histamine-induced rat paw edema. Conclusion: These results highlight the potential of peptide 2 in the prevention and treatment of various allergic diseases mediated by mast cell activation.

Original language	English
Article number	9
Journal	International Journal of Peptide Research and Therapeutics
Volume	31
Issue number	1
DOIs	https://doi.org/10.1007/s10989-024-10670-2
State	Published - 2025/01

Keywords

Anti-allergic agent
Biotinylated peptide
D-amino acid
Degranulation
Histamine
Mast cell

ASJC Scopus subject areas

Analytical Chemistry
Bioengineering
Biochemistry
Molecular Medicine
Drug Discovery

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10.1007/s10989-024-10670-2

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Ohira, M., Uwamizu, A., Hori, K., Obinata, Y., Uta, D., Aoki, J., Ebina, K., Matsumoto, T., & Sato, A. (2025). Biotinylated Heptapeptides with D-amino Acids Suppress Allergic Reactions by Inhibiting Mast Cell Activation and Antagonizing the Histamine Receptor. International Journal of Peptide Research and Therapeutics, 31(1), Article 9. https://doi.org/10.1007/s10989-024-10670-2

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title = "Biotinylated Heptapeptides with D-amino Acids Suppress Allergic Reactions by Inhibiting Mast Cell Activation and Antagonizing the Histamine Receptor",

abstract = "Background: Mast cells play an important role in allergic reactions by releasing potent mediators, including histamine and platelet-activating factor (PAF), upon activation. We recently reported that a biotinylated heptapeptide (peptide 2), D-Lys(Biotinyl)-Trp-Tyr-Lys-Asp-Gly-Asp, which is highly stable in the plasma, inhibits PAF bioactivity and anaphylactic hypothermia in vivo. However, the effects of this peptide on allergy induction by mast cells have not been investigated. Methods and Results: Several biotinylated heptapeptides, including peptide 2, inhibited IgE/antigen-stimulated degranulation in RBL-2H3 cells. Peptide 2 also markedly inhibited the degranulation induced by calcium ionophore A23187. All peptides (peptide 1, 2 and 3) inhibited activating stimuli-induced increase in intracellular Ca2+ levels. The transforming growth factor-alpha shedding assay indicated that peptide 2 antagonized against the histamine H1 receptor. Furthermore, peptide 2 inhibited histamine-induced rat paw edema. Conclusion: These results highlight the potential of peptide 2 in the prevention and treatment of various allergic diseases mediated by mast cell activation.",

keywords = "Anti-allergic agent, Biotinylated peptide, D-amino acid, Degranulation, Histamine, Mast cell",

author = "Makoto Ohira and Akiharu Uwamizu and Keita Hori and Yumi Obinata and Daisuke Uta and Junken Aoki and Keiichi Ebina and Tsukasa Matsumoto and Akira Sato",

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doi = "10.1007/s10989-024-10670-2",

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Ohira, M, Uwamizu, A, Hori, K, Obinata, Y, Uta, D, Aoki, J, Ebina, K, Matsumoto, T & Sato, A 2025, 'Biotinylated Heptapeptides with D-amino Acids Suppress Allergic Reactions by Inhibiting Mast Cell Activation and Antagonizing the Histamine Receptor', International Journal of Peptide Research and Therapeutics, vol. 31, no. 1, 9. https://doi.org/10.1007/s10989-024-10670-2

TY - JOUR

T1 - Biotinylated Heptapeptides with D-amino Acids Suppress Allergic Reactions by Inhibiting Mast Cell Activation and Antagonizing the Histamine Receptor

AU - Ohira, Makoto

AU - Uwamizu, Akiharu

AU - Hori, Keita

AU - Obinata, Yumi

AU - Uta, Daisuke

AU - Aoki, Junken

AU - Ebina, Keiichi

AU - Matsumoto, Tsukasa

AU - Sato, Akira

N1 - Publisher Copyright: © The Author(s), under exclusive licence to Springer Nature B.V. 2024.

PY - 2025/1

Y1 - 2025/1

N2 - Background: Mast cells play an important role in allergic reactions by releasing potent mediators, including histamine and platelet-activating factor (PAF), upon activation. We recently reported that a biotinylated heptapeptide (peptide 2), D-Lys(Biotinyl)-Trp-Tyr-Lys-Asp-Gly-Asp, which is highly stable in the plasma, inhibits PAF bioactivity and anaphylactic hypothermia in vivo. However, the effects of this peptide on allergy induction by mast cells have not been investigated. Methods and Results: Several biotinylated heptapeptides, including peptide 2, inhibited IgE/antigen-stimulated degranulation in RBL-2H3 cells. Peptide 2 also markedly inhibited the degranulation induced by calcium ionophore A23187. All peptides (peptide 1, 2 and 3) inhibited activating stimuli-induced increase in intracellular Ca2+ levels. The transforming growth factor-alpha shedding assay indicated that peptide 2 antagonized against the histamine H1 receptor. Furthermore, peptide 2 inhibited histamine-induced rat paw edema. Conclusion: These results highlight the potential of peptide 2 in the prevention and treatment of various allergic diseases mediated by mast cell activation.

AB - Background: Mast cells play an important role in allergic reactions by releasing potent mediators, including histamine and platelet-activating factor (PAF), upon activation. We recently reported that a biotinylated heptapeptide (peptide 2), D-Lys(Biotinyl)-Trp-Tyr-Lys-Asp-Gly-Asp, which is highly stable in the plasma, inhibits PAF bioactivity and anaphylactic hypothermia in vivo. However, the effects of this peptide on allergy induction by mast cells have not been investigated. Methods and Results: Several biotinylated heptapeptides, including peptide 2, inhibited IgE/antigen-stimulated degranulation in RBL-2H3 cells. Peptide 2 also markedly inhibited the degranulation induced by calcium ionophore A23187. All peptides (peptide 1, 2 and 3) inhibited activating stimuli-induced increase in intracellular Ca2+ levels. The transforming growth factor-alpha shedding assay indicated that peptide 2 antagonized against the histamine H1 receptor. Furthermore, peptide 2 inhibited histamine-induced rat paw edema. Conclusion: These results highlight the potential of peptide 2 in the prevention and treatment of various allergic diseases mediated by mast cell activation.

KW - Anti-allergic agent

KW - Biotinylated peptide

KW - D-amino acid

KW - Degranulation

KW - Histamine

KW - Mast cell

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DO - 10.1007/s10989-024-10670-2

M3 - 学術論文

AN - SCOPUS:85209563194

SN - 1573-3149

VL - 31

JO - International Journal of Peptide Research and Therapeutics

JF - International Journal of Peptide Research and Therapeutics

IS - 1

M1 - 9

ER -

Biotinylated Heptapeptides with D-amino Acids Suppress Allergic Reactions by Inhibiting Mast Cell Activation and Antagonizing the Histamine Receptor

Abstract

Keywords

ASJC Scopus subject areas

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