Colquhoun David
Department of Pharmacology, University College London, London, UK.
Trends Pharmacol Sci. 2007 Dec;28(12):608-14. doi: 10.1016/j.tips.2007.09.011. Epub 2007 Nov 26.
It is almost 60 years since Heinz Schild devised a method that allowed measurement of a genuine physical quantity, the equilibrium constant for binding of a competitive antagonist. The clever bit was that the measurements could be made using responses from tissues despite the fact that little or nothing was known about how the agonist worked. Since then, attempts have been made to generalise the Schild equation, but they are all based on false premises. It turns out that generalisation is usually not needed. His original simple result is still valid in cases where several agonist molecules must be bound to produce a response, even if the agonist binding sites interact or are not identical.
自海因茨·席尔德设计出一种方法以来,已经过去了近60年,该方法能够测量一个真正的物理量——竞争性拮抗剂结合的平衡常数。巧妙之处在于,尽管对激动剂的作用方式知之甚少,但仍可利用组织的反应进行测量。从那时起,人们试图对席尔德方程进行推广,但这些尝试都基于错误的前提。事实证明,通常并不需要进行推广。即使激动剂结合位点相互作用或不相同,在几个激动剂分子必须结合才能产生反应的情况下,他最初的简单结果仍然有效。