3-碘甲状腺胺是一种微量胺相关受体激动剂,通过大鼠脑小动脉中的Epac2通过CaMK II调节细胞内Ca2+的增加。

IF 1.3 4区 医学 Q4 MEDICINE, RESEARCH & EXPERIMENTAL
Wakana Sakanoue, Takuya Yokoyama, Masato Hirakawa, Satsuki Maesawa, Kenichi Sato, Tomoyuki Saino
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引用次数: 1

摘要

神经系统中的微量胺(TA)与TA相关受体(TAARs)结合,并参与单胺能功能的调节。在TAAR亚型中,TAAR1与神经系统疾病的发展有关,如精神分裂症。本研究利用细胞内Ca2+([Ca2+]i)浓度的波动作为收缩反应的指标,研究了TAAR1激动剂3-碘甲状腺胺(T1AM)对脑小动脉的影响。在脑小动脉中,大多数TAAR激动剂没有增加血管平滑肌细胞的[Ca2+]i,而只有T1AM升高了血管平滑肌细胞中的[Ca2++]i。这种增加涉及通过T型Ca2+通道的细胞外Ca2+内流,以及肌醇三磷酸和赖氨酸受体介导的细胞内储存的Ca2+释放。cAMP传感器、由cAMP(Epac)2直接激活的交换蛋白和钙调蛋白激酶(CaMK)II的抑制强烈抑制Ca2+升高。本研究表明,T1AM不仅如前所述作用于TAAR1受体,还作用于其他G蛋白偶联受体和/或信号转导系统,以增加脑小动脉平滑肌细胞中的细胞内Ca2+。这些结果表明,在临床实践中使用T1AM时,应注意血压的早期升高。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
3-Iodothyronamine, a trace amine-associated receptor agonist, regulates intracellular Ca2+ increases via CaMK II through Epac2 in rat cerebral arterioles.

Trace amines (TAs) in the nervous system bind to TA-associated receptors (TAARs) and are involved in the regulation of monoaminergic functions. Among TAAR subtypes, TAAR1 has been implicated in the development of neurological disorders, such as schizophrenia. The present study investigated the effects of the TAAR1 agonist, 3-iodothyronamine (T1AM) on cerebral arterioles using fluctuations in the intracellular concentration of Ca2+ ([Ca2+]i) as an index of contractile responses. In cerebral arterioles, most of the TAAR agonists did not increase [Ca2+]i, while only T1AM elevated [Ca2+]i in vascular smooth muscle cells. This increase involved extracellular Ca2+ influx through T-type Ca2+ channels and inositol trisphosphate- and ryanodine-receptor-mediated Ca2+ release from intracellular stores. The inhibition of the cAMP sensor, exchange protein directly activated by cAMP (Epac) 2, and calmodulin kinase (CaMK) II strongly inhibited Ca2+ elevations. The present study revealed that T1AM acted not only on the TAAR1 receptor as previously suggested, but also on other G-protein coupled receptors and/or signal transduction systems to increase intracellular Ca2+ in cerebral arteriole smooth muscle cells. These results suggest that when using T1AM in clinical practice, attention should be paid to the early rise in blood pressure.

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来源期刊
Biomedical Research-tokyo
Biomedical Research-tokyo 医学-医学:研究与实验
CiteScore
2.40
自引率
0.00%
发文量
19
审稿时长
>12 weeks
期刊介绍: Biomedical Research is peer-reviewed International Research Journal . It was first launched in 1990 as a biannual English Journal and later became triannual. From 2008 it is published in Jan-Apr/ May-Aug/ Sep-Dec..
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