Alkozi Hanan Awad, Pintor Jesús
Department of Biochemistry, Faculty of Optometry, Universidad Complutense de Madrid, C/ Arcos de Jalón 118, E281037 Madrid, Spain.
Department of Biochemistry, Faculty of Optometry, Universidad Complutense de Madrid, C/ Arcos de Jalón 118, E281037 Madrid, Spain.
Exp Eye Res. 2015 Jul;136:34-7. doi: 10.1016/j.exer.2015.04.019. Epub 2015 Apr 29.
Melatonin is a neurohormone mainly produced in the pineal gland; nevertheless, various ocular structures such as the ciliary body, lens and the retina produce it. One of the roles of melatonin in the eye is the modulation of intraocular pressure, although little is known about the mechanisms that causes its presence in the aqueous humour. TRPV4 is a membrane channel which is activated by both physical and chemical stimuli. Therefore, this channel is sensitive to osmotic and hydrostatic pressure. As a consequence, TRPV4 results as an interesting candidate to study the relation between the activation of the TRPV4 channel and the production of melatonin. In this sense we have studied the role of the TRPV4 agonist GSK1016790A to modulate the production of melatonin in a cell line derived from human non-pigmented ciliary epithelial cells. The stimulation of the TRPV4 produced an increase in the extracellular melatonin levels changing from 8.5 ± 0.6 nM/well/30 min (control) to 23.3 ± 2.1 nM/well/30 min after 10 nM GSK1016790A application, this action being blocked by the selective antagonist RN 1734. The activation of the TRPV4 by GSK1016790A permitted to observe a melatonin increase which was concentration-dependent, and provided a pD2 value of -8.5 ± 0.1 (EC50 of 3.0 nM). In conclusion, the activation of the TRPV4 present in human non-pigmented ciliary epithelial cells can modulate the presence of extracellular melatonin, this being of relevance since this substance controls the dynamics of the aqueous humour.
褪黑素是一种主要由松果体产生的神经激素；然而，睫状体、晶状体和视网膜等各种眼部结构也能产生褪黑素。褪黑素在眼睛中的作用之一是调节眼压，尽管对于其在房水中存在的机制知之甚少。瞬时受体电位香草酸亚型4（TRPV4）是一种膜通道，可被物理和化学刺激激活。因此，该通道对渗透压和流体静压敏感。因此，TRPV4成为研究TRPV4通道激活与褪黑素产生之间关系的一个有趣候选对象。从这个意义上讲，我们研究了TRPV4激动剂GSK1016790A对源自人非色素睫状上皮细胞的细胞系中褪黑素产生的调节作用。TRPV4的刺激使细胞外褪黑素水平升高，从8.5±0.6 nM/孔/30分钟（对照）在应用10 nM GSK1016790A后变为23.3±2.1 nM/孔/30分钟，这种作用被选择性拮抗剂RN 1734阻断。GSK1016790A对TRPV4的激活使得观察到褪黑素增加呈浓度依赖性，并提供了-8.5±0.1的pD2值（EC50为3.0 nM）。总之，人非色素睫状上皮细胞中TRPV4的激活可调节细胞外褪黑素的存在，这具有重要意义，因为这种物质控制房水的动态。
