Hypotaurine is a precursor for the biosynthesis of taurine and is an endogenous inhibitory amino acid of the glycine receptor [1]. Hypotaurine inhibits the GABA transporters 1 (GAT1), 2 (GAT2), 3 (GAT3), and 4 (GAT4) in mice (IC50 values are 170, 240, 4.9, and 8.1μM respectively) and GAT1, 2, and 3 in rats (IC50 values are 1010, 52, and 73μM respectively) for the uptake of GABA [2]. As an antioxidant, Hypotaurine can effectively eliminate free radicals and reactive oxygen species [3].
In vitro, Hypotaurine (1mM; 24h) significantly reduced the concentration of hydroxyl radicals in rat placental trophoblast cells (TR-TBT 18d-1) treated with H2O2, and had a protective effect against H2O2-induced oxidative damage [4]. Under high chloride conditions, Hypotaurine (30-3000μM; 100s) increased the inward current or upward deflection of membrane potential in glial cells (SG) neurons in the immature mouse tail trigeminal nucleus (Vc) in a concentration-dependent manner, with EC50 values of 663.8 and 337.6μM respectively [5].
In vivo, in rats subjected to tail swinging, paw pressing, and formalin test, Hypotaurine (100, 200, 400, and 600μg/10μL; intrathecal injection) prolonged the tail flick latency in a dose-dependent manner, alleviated mechanical hyperalgesia and thermal hyperalgesia [6]. Hypotaurine (2.4mM/kg/2mL; intraperitoneal injection) pretreatment significantly attenuated the increase in ALT, AST, and LDH activities in rat plasma induced by acetaminophen (APAP), as well as the decrease in GR, GST, and GCS activities and the consumption of GSSG in the liver [7].
References:
[1] Green TR, Fellman JH, Eicher AL, Pratt KL. Antioxidant role and subcellular location of hypotaurine and taurine in human neutrophils. Biochim Biophys Acta. 1991;1073(1):91-97.
[2] Kragler, A., Höfner, G., and Wanner, K.T. Novel parent structures for inhibitors of the murine GABA transporters mGAT3 and mGAT4. Eur. J. Pharmacol. 519(1-2), 43-47 (2005).
[3] Aruoma O I, Halliwell B, Hoey B M, et al. The antioxidant action of taurine, hypotaurine and their metabolic precursors[J]. Biochemical Journal, 1988, 256(1): 251-255.
[4] Nishimura T, Duereh M, Sugita Y, et al. Protective effect of hypotaurine against oxidative stress-induced cytotoxicity in rat placental trophoblasts. Placenta. 2015;36(6):693-698.
[5] Oh SM, Bhattarai JP, Han SK, Park SJ. Effects of hypotaurine on substantia gelatinosa neurons of the trigeminal subnucleus caudalis in immature mice. Amino Acids. 2016;48(12):2843-2853.
[6] Hara K, Nakamura M, Haranishi Y, Terada T, Kataoka K, Sata T. Antinociceptive effect of intrathecal administration of hypotaurine in rat models of inflammatory and neuropathic pain. Amino Acids. 2012;43(1):397-404.
[7] Acharya M, Lau-Cam CA. Comparison of the protective actions of N-acetylcysteine, hypotaurine and taurine against acetaminophen-induced hepatotoxicity in the rat. J Biomed Sci. 2010;17 Suppl 1(Suppl 1):S35. Published 2010 Aug 24.
Hypotaurine是牛磺酸生物合成的前体，是甘氨酸受体（glycine receptor）的内源性抑制性氨基酸 [1]。Hypotaurine抑制小鼠的GABA转运蛋白1（GAT1）、GAT2、GAT3和GAT4（IC50值分别为170、240、4.9和8.1μM）以及大鼠的GAT1、GAT2和GAT3（IC50值分别为1010、52和73μM）对GABA的摄取 [2]。Hypotaurine作为抗氧化剂能够有效清除自由基和活性氧 [3]。
在体外，Hypotaurine（1mM; 24h）显著降低了H2O2处理的大鼠胎盘滋养细胞（TR-TBT 18d-1）的羟基自由基的浓度，对H2O2诱导的氧化损伤具有保护作用 [4]。在高氯条件下，Hypotaurine（30-3000μM; 100s）以浓度依赖性方式增加了在未成熟小鼠尾部三叉神经核（Vc）的胶质物（SG）神经元中膜电位的向内电流或向上偏转，EC50分别为663.8和337.6μM [5]。
在体内，在进行尾部摆动、爪子按压以及福尔马林测试的大鼠中，Hypotaurine（100, 200, 400和600μg/10μL; 鞘内注射）以剂量依赖性方式延长了尾部弹动潜伏期，缓解了机械性痛觉异常和热痛觉过敏 [6]。Hypotaurine（2.4mM/kg/2mL; i.p.）预处理显著减弱了乙酰氨基酚（APAP）诱导的大鼠血浆中ALT、AST和LDH活性的升高，GR、GST和GCS活性的降低和肝脏GSSG的消耗 [7]。