Small-molecule non-peptide antagonists of the PACAP receptor attenuate acute restraint stress-induced anxiety-like behaviors in mice

Yusuke Shintani; Yui Yamano; Manato kuta; Rei Takeshita; Kazuhiro Takuma; Takuya Okada; Naoki Toyooka; Ichiro Takasaki; Atsuro Miyata; Takashi Kurihara; Hitoshi Hashimoto; Atsuko Hayata-Takano

doi:10.1016/j.bbrc.2022.09.079

Small-molecule non-peptide antagonists of the PACAP receptor attenuate acute restraint stress-induced anxiety-like behaviors in mice

Yusuke Shintani, Yui Yamano, Manato kuta, Rei Takeshita, Kazuhiro Takuma, Takuya Okada, Naoki Toyooka, Ichiro Takasaki, Atsuro Miyata, Takashi Kurihara, Hitoshi Hashimoto^*, Atsuko Hayata-Takano^*

^*Corresponding author for this work

Life Sciences and Bioengineering

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

4 Scopus citations

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved pleiotropic neuropeptide, implicated in emotional stress responses and anxiety-related disorders. Here, we examined whether our recently developed small-molecule non-peptide PACAP receptor antagonists could ameliorate anxiety-like behaviors induced by acute restraint stress in mice. The antagonists PA-9 and its derivative PA-915 improved anxiety-like behaviors in mice subjected to restraint stress. An anxiolytic effect was observed with single acute dose, suggesting their fast-acting properties. PA-915 demonstrated a statistically significant anxiolytic effect whereas fluoxetine did not. These results indicate the potential of PAC1 antagonists as a novel treatment for anxiety.

Original language	English
Pages (from-to)	146-151
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	631
DOIs	https://doi.org/10.1016/j.bbrc.2022.09.079
State	Published - 2022/11/26

Keywords

Acute stress
Anxiolytic effect
PAC1 receptor
PACAP
Pituitary adenylate cyclase-activating polypeptide
Small-molecule non-peptide antagonist

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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Shintani, Y., Yamano, Y., kuta, M., Takeshita, R., Takuma, K., Okada, T., Toyooka, N., Takasaki, I., Miyata, A., Kurihara, T., Hashimoto, H., & Hayata-Takano, A. (2022). Small-molecule non-peptide antagonists of the PACAP receptor attenuate acute restraint stress-induced anxiety-like behaviors in mice. Biochemical and Biophysical Research Communications, 631, 146-151. https://doi.org/10.1016/j.bbrc.2022.09.079

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title = "Small-molecule non-peptide antagonists of the PACAP receptor attenuate acute restraint stress-induced anxiety-like behaviors in mice",

abstract = "Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved pleiotropic neuropeptide, implicated in emotional stress responses and anxiety-related disorders. Here, we examined whether our recently developed small-molecule non-peptide PACAP receptor antagonists could ameliorate anxiety-like behaviors induced by acute restraint stress in mice. The antagonists PA-9 and its derivative PA-915 improved anxiety-like behaviors in mice subjected to restraint stress. An anxiolytic effect was observed with single acute dose, suggesting their fast-acting properties. PA-915 demonstrated a statistically significant anxiolytic effect whereas fluoxetine did not. These results indicate the potential of PAC1 antagonists as a novel treatment for anxiety.",

keywords = "Acute stress, Anxiolytic effect, PAC1 receptor, PACAP, Pituitary adenylate cyclase-activating polypeptide, Small-molecule non-peptide antagonist",

author = "Yusuke Shintani and Yui Yamano and Manato kuta and Rei Takeshita and Kazuhiro Takuma and Takuya Okada and Naoki Toyooka and Ichiro Takasaki and Atsuro Miyata and Takashi Kurihara and Hitoshi Hashimoto and Atsuko Hayata-Takano",

note = "Publisher Copyright: {\textcopyright} 2022",

year = "2022",

month = nov,

day = "26",

doi = "10.1016/j.bbrc.2022.09.079",

language = "英語",

volume = "631",

pages = "146--151",

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Shintani, Y, Yamano, Y, kuta, M, Takeshita, R, Takuma, K, Okada, T , Toyooka, N , Takasaki, I, Miyata, A, Kurihara, T, Hashimoto, H & Hayata-Takano, A 2022, 'Small-molecule non-peptide antagonists of the PACAP receptor attenuate acute restraint stress-induced anxiety-like behaviors in mice', Biochemical and Biophysical Research Communications, vol. 631, pp. 146-151. https://doi.org/10.1016/j.bbrc.2022.09.079

TY - JOUR

T1 - Small-molecule non-peptide antagonists of the PACAP receptor attenuate acute restraint stress-induced anxiety-like behaviors in mice

AU - Shintani, Yusuke

AU - Yamano, Yui

AU - kuta, Manato

AU - Takeshita, Rei

AU - Takuma, Kazuhiro

AU - Okada, Takuya

AU - Toyooka, Naoki

AU - Takasaki, Ichiro

AU - Miyata, Atsuro

AU - Kurihara, Takashi

AU - Hashimoto, Hitoshi

AU - Hayata-Takano, Atsuko

PY - 2022/11/26

Y1 - 2022/11/26

N2 - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved pleiotropic neuropeptide, implicated in emotional stress responses and anxiety-related disorders. Here, we examined whether our recently developed small-molecule non-peptide PACAP receptor antagonists could ameliorate anxiety-like behaviors induced by acute restraint stress in mice. The antagonists PA-9 and its derivative PA-915 improved anxiety-like behaviors in mice subjected to restraint stress. An anxiolytic effect was observed with single acute dose, suggesting their fast-acting properties. PA-915 demonstrated a statistically significant anxiolytic effect whereas fluoxetine did not. These results indicate the potential of PAC1 antagonists as a novel treatment for anxiety.

AB - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a highly conserved pleiotropic neuropeptide, implicated in emotional stress responses and anxiety-related disorders. Here, we examined whether our recently developed small-molecule non-peptide PACAP receptor antagonists could ameliorate anxiety-like behaviors induced by acute restraint stress in mice. The antagonists PA-9 and its derivative PA-915 improved anxiety-like behaviors in mice subjected to restraint stress. An anxiolytic effect was observed with single acute dose, suggesting their fast-acting properties. PA-915 demonstrated a statistically significant anxiolytic effect whereas fluoxetine did not. These results indicate the potential of PAC1 antagonists as a novel treatment for anxiety.

KW - Acute stress

KW - Anxiolytic effect

KW - PAC1 receptor

KW - PACAP

KW - Pituitary adenylate cyclase-activating polypeptide

KW - Small-molecule non-peptide antagonist

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U2 - 10.1016/j.bbrc.2022.09.079

DO - 10.1016/j.bbrc.2022.09.079

M3 - 学術論文

C2 - 36194909

AN - SCOPUS:85139311897

SN - 0006-291X

VL - 631

SP - 146

EP - 151

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

ER -

Small-molecule non-peptide antagonists of the PACAP receptor attenuate acute restraint stress-induced anxiety-like behaviors in mice

Abstract

Keywords

ASJC Scopus subject areas

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