Tribute to Prof. Geoffrey Burnstock: transition of purinergicsignaling to drug discovery.

Geoffrey Burnstock made a chance observation early in his research career that did not fit the conventional scientific dogma-non-noradrenergic, non-cholinergic (NANC) nerves. Instead of rejecting these as an artifact, he followed their logical course to characterize the actions of extracellular ATP on nerves and muscles, eventually founding a large branch of pharmacology around purinergic signaling. The solid proof that validated his concept and dismissed many detractors was the cloning of seven ionotropic P2X receptors and eight metabotropic P2Y receptors, which are expressed in some combination in every tissue and organ. Given the broad importance of this signaling system in biology, medicinal chemists, inspired by Burnstock, began creating synthetic agonists and antagonists for these purinergic receptors. Various ligands have advanced to clinical trials, for disorders of the immune, nervous, cardiovascular, and other systems, and a few are already approved. Thus, medically important approaches have been derived from Burnstock's original pharmacological concepts and his constant guiding of the course of the field. The therapeutic potential of modulators of purinergic signaling is vast.