Involvement of Cav3.2 T-type Ca2+ channels and cystathionine-β-synthase in colitis-related visceral hypersensitivity in mice

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences Pub Date : 2024-09-21 DOI:10.1016/j.jphs.2024.09.003

Maho Tsubota , Yuriko Iba , Tsukasa Hatakeyama , Myu Honda , Yoshihito Kasanami , Fumiko Sekiguchi , Atsushi Kawase , Takuya Okada , Naoki Toyooka , Atsufumi Kawabata

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引用次数: 0

Abstract

We tested the hypothesis that Ca_v3.2 T-type Ca²⁺ channels, which can be rebooted by sulfides from Zn²⁺ inhibition under physiological conditions, and sulfide-generating enzymes including cystathionine-β-synthase (CBS) would participate in the colitis-related visceral pain in mice treated with 2,4,6-trinitrobenzene sulfonic acid (TNBS). The visceral hypersensitivity following TNBS-induced colitis was abolished by an inhibitor or genetic deletion of Ca_v3.2 and by a CBS inhibitor, and accompanied by CBS upregulation in the colon. Our data thus suggest that the enhanced activity of Ca_v3.2 brought about by sulfides generated by upregulated CBS is involved in the colitis-related visceral hypersensitivity.

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Cav3.2 T 型 Ca2+ 通道和胱硫醚-β-合成酶参与小鼠结肠炎相关的内脏超敏反应

我们假设，在生理条件下，Cav3.2 T 型 Ca2+ 通道可通过 Zn2+ 抑制硫化物而重新启动，而硫化物生成酶包括胱硫醚-β-合成酶（CBS）将参与 2,4,6-三硝基苯磺酸（TNBS）治疗小鼠结肠炎相关的内脏疼痛。Cav3.2抑制剂或基因缺失以及CBS抑制剂均可消除TNBS诱导的结肠炎引起的内脏超敏反应，同时结肠中的CBS也会上调。因此，我们的数据表明，CBS 上调产生的硫化物导致的 Cav3.2 活性增强参与了结肠炎相关的内脏超敏反应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of pharmacological sciences 医学-药学

CiteScore

6.20

自引率

2.90%

发文量

104

审稿时长

31 days

期刊介绍： Journal of Pharmacological Sciences (JPS) is an international open access journal intended for the advancement of pharmacological sciences in the world. The Journal welcomes submissions in all fields of experimental and clinical pharmacology, including neuroscience, and biochemical, cellular, and molecular pharmacology for publication as Reviews, Full Papers or Short Communications. Short Communications are short research article intended to provide novel and exciting pharmacological findings. Manuscripts concerning descriptive case reports, pharmacokinetic and pharmacodynamic studies without pharmacological mechanism and dose-response determinations are not acceptable and will be rejected without peer review. The ethnopharmacological studies are also out of the scope of this journal. Furthermore, JPS does not publish work on the actions of biological extracts unknown chemical composition.