Novel technique to determine the pKA of clonidine at prejunctional α2-adrenoceptors in cardiac and vascular sympathetic transmission

Abstract

Analytical pharmacology draws heavily on the concept of equilibrium of agonist and silent antagonist concentrations competing at a specific receptor site. This condition breaks down in nerve transmission when transmitter release is inhibited by prejunctional α2-adrenoceptors activated by an agonist such as clonidine. We have developed a method that allows the agonist dissociation constant KA of clonidine to be determined in a robust isolated right atrial assay of mouse, rat and guinea pig. By applying low numbers of field pulses 1–4 to prevent autoinhibitory feedback, clonidine shifted the nerve pulse stimulation-tachycardia curves to the right. These peak responses to field pulses were equa..