A Chemically Stable Photocaged Noradrenaline.

IF 4.1 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Stanley A Buczynski, Amy Li, Janie Chang-Weinberg, Shayra S Nawsheen, Matthew R Banghart
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引用次数: 0

Abstract

Photoactivatable neurotransmitters provide spatiotemporally precise experimenter control over endogenous receptor activation in living tissue. The resulting optical stimulus-neuronal response relationship provides a sensitive assay that can drive quantitative studies into receptor signaling. Here, we report a photocaged derivative of the prominent catecholamine neurotransmitter noradrenaline (NA). Appending a carboxynitroveratryl (CNV) caging group to the 4-hydroxyl of the catechol group produced CNV-NA, which displays good aqueous solubility and chemical stability. We verified CNV-NA's lack of activity at α1B- and β2-adrenoreceptors expressed in HEK cells using a live-cell cAMP assay. We validated CNV-NA photoactivation at native α2-adrenoreceptors in brain slices of rat locus coeruleus using whole cell electrophysiological recordings. Monitoring the stereotyped outward current response to repeated CNV-NA photoactivation revealed that the neuropeptide substance P suppresses α2-adrenoreceptor signaling in locus coeruleus neurons. This work adds a new reagent to the growing library of photocaged neuroactive ligands, thereby expanding the scope and applications of photopharmacology.

化学稳定的照相笼化去甲肾上腺素。
可光激活的神经递质提供了对活组织内源性受体激活的时空精确的实验控制。由此产生的光刺激-神经元反应关系提供了一种敏感的分析方法,可以驱动受体信号的定量研究。在这里,我们报告了一种突出的儿茶酚胺神经递质去甲肾上腺素(NA)的光笼衍生物。在邻苯二酚基团的4-羟基上加入一个羧硝基戊戊基(CNV)笼化基团生成CNV- na,具有良好的水溶性和化学稳定性。我们使用活细胞cAMP实验验证了CNV-NA在HEK细胞中表达的α1B-和β2肾上腺素受体缺乏活性。我们利用全细胞电生理记录验证了CNV-NA在大鼠蓝斑区脑切片中对天然α2-肾上腺素受体的光激活。监测CNV-NA重复光激活的刻板外向电流反应表明,神经肽物质P抑制蓝斑神经元α2-肾上腺素受体信号传导。这项工作为不断增长的光笼神经活性配体库增加了一种新的试剂,从而扩大了光药理学的范围和应用。
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来源期刊
ACS Chemical Neuroscience
ACS Chemical Neuroscience BIOCHEMISTRY & MOLECULAR BIOLOGY-CHEMISTRY, MEDICINAL
CiteScore
9.20
自引率
4.00%
发文量
323
审稿时长
1 months
期刊介绍: ACS Chemical Neuroscience publishes high-quality research articles and reviews that showcase chemical, quantitative biological, biophysical and bioengineering approaches to the understanding of the nervous system and to the development of new treatments for neurological disorders. Research in the journal focuses on aspects of chemical neurobiology and bio-neurochemistry such as the following: Neurotransmitters and receptors Neuropharmaceuticals and therapeutics Neural development—Plasticity, and degeneration Chemical, physical, and computational methods in neuroscience Neuronal diseases—basis, detection, and treatment Mechanism of aging, learning, memory and behavior Pain and sensory processing Neurotoxins Neuroscience-inspired bioengineering Development of methods in chemical neurobiology Neuroimaging agents and technologies Animal models for central nervous system diseases Behavioral research
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