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牛磺酸通过视网膜神经元中的代谢型途径激活延迟整流钾通道。

Taurine activates delayed rectifier Kv channels via a metabotropic pathway in retinal neurons.

机构信息

Department of Biomedical Science, Charles E Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL 33431, USA.

出版信息

J Physiol. 2013 Jan 1;591(1):123-32. doi: 10.1113/jphysiol.2012.243147. Epub 2012 Oct 8.

Abstract

Taurine is one of the most abundant amino acids in the retina, throughout the CNS, and in heart and muscle cells. In keeping with its broad tissue distribution, taurine serves as a modulator of numerous basic processes, such as enzyme activity, cell development, myocardial function and cytoprotection. Despite this multitude of functional roles, the precise mechanism underlying taurine's actions has not yet been identified. In this study we report findings that indicate a novel role for taurine in the regulation of voltage-gated delayed rectifier potassium (K(V)) channels in retinal neurons by means of a metabotropic receptor pathway. The metabotropic taurine response was insensitive to the Cl(-) channel blockers, picrotoxin and strychnine, but it was inhibited by a specific serotonin 5-HT(2A) receptor antagonist, MDL11939. Moreover, we found that taurine enhanced K(V) channels via intracellular protein kinase C-mediated pathways. When 5-HT(2A) receptors were expressed in human embryonic kidney cells, taurine and AL34662, a non-specific 5-HT(2) receptor activator, produced a similar regulation of K(IR) channels. In sum, this study provides new evidence that taurine activates a serotonin system, apparently via 5-HT(2A) receptors and related intracellular pathways.

摘要

牛磺酸是视网膜、整个中枢神经系统以及心脏和肌肉细胞中含量最丰富的氨基酸之一。牛磺酸广泛分布于组织中,作为多种基本过程的调节剂,如酶活性、细胞发育、心肌功能和细胞保护。尽管具有多种功能作用,但牛磺酸作用的确切机制尚未确定。在这项研究中,我们报告了发现表明牛磺酸通过代谢型受体途径在视网膜神经元中调节电压门控延迟整流钾 (K(V)) 通道方面具有新的作用。代谢型牛磺酸反应对 Cl(-) 通道阻滞剂(如胡椒碱和士的宁)不敏感,但对特定的 5-羟色胺 5-HT(2A) 受体拮抗剂 MDL11939 敏感。此外,我们发现牛磺酸通过细胞内蛋白激酶 C 介导的途径增强 K(V) 通道。当 5-HT(2A) 受体在人胚肾细胞中表达时,牛磺酸和 AL34662(一种非特异性 5-HT(2) 受体激活剂)对 K(IR) 通道产生类似的调节作用。总之,这项研究提供了新的证据,表明牛磺酸通过 5-HT(2A) 受体和相关的细胞内途径激活 5-羟色胺系统。

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