Departamento de Fisiología, Universidad Nacional Autónoma de México, DF México.
Channels (Austin). 2011 Jan-Feb;5(1):56-64. doi: 10.4161/chan.5.1.13972. Epub 2011 Jan 1.
Celecoxib is a drug designed to selectively inhibit COX-2, an inflammation-inducible cyclooxygenase isoform, over the constitutively expressed COX-1 isoform. In addition to this selective inhibition it is now known that celecoxib exerts a variety of effects on several types of ion channels, thus producing secondary physiological effects. In this work we demonstrate that at therapeutically relevant concentrations celecoxib interacts with Shab K(+) channels specifically promoting a fast inactivation gating (without blocking the pore or significantly affecting other gating processes). At least two celecoxib molecules bind to each channel promoting a fast inactivation that develops from both open and closed states. Channel inactivation in turn causes a reduction of the size of I(K). Taken together, our observations show that in addition to its intended therapeutic target celecoxib is a useful tool to further study the mechanism of Shab channel inactivation.
塞来昔布是一种旨在选择性抑制 COX-2 的药物，COX-2 是一种炎症诱导的环氧化酶同工型，超过组成型表达的 COX-1 同工型。除了这种选择性抑制作用外，现在已知塞来昔布对几种类型的离子通道产生多种作用，从而产生次要的生理作用。在这项工作中，我们证明在治疗相关浓度下，塞来昔布与 Shab K(+) 通道特异性相互作用，特别促进快速失活门控（不阻断孔或显著影响其他门控过程）。至少有两个塞来昔布分子结合到每个通道上，促进从开放和关闭状态发展而来的快速失活。通道失活反过来导致 I(K)的减小。总之，我们的观察表明，除了其预期的治疗靶点外，塞来昔布还是进一步研究 Shab 通道失活机制的有用工具。
