Insurmountable AT1 receptor antagonism: Message in a model? [2]

Abstract

We read with great interest the recent letter asserting the need for different antagonist receptor binding states to explain insurmountable antagonism at the angiotensin AT1 receptor 1. There is no disagreement on both the importance of slow antagonist dissociation for insurmountability and the utility of kinetic rather than equilibrium models. However, we believe that the model comparison presented is insufficient to declare a need for different antagonist binding states of the receptor.