The biologic actions of extracellular adenosine triphosphate

The study of the biologic effects of extracellular ATP is rapidly progressing from cataloging the integrated biologic responses of isolated tissues to characterizing the biochemical basis of signal transduction in isolated cells. Clearly, many fundamental issues remain; these include the classification of receptor subtypes, identification of defined or new signal-transduction pathways, generation of specific high-affinity ligands for the various ATP receptor subtypes, and ultimately, the development of protocols for the identification, isolation, cloning, and physicochemical characterization of the receptor moities per se. Such work will be essential for developing selective ATP-receptor antagonists. Such antagonists, in turn, will facilitate evaluation of the role of these receptors in physiological and/or pathological processes. A possible therapeutic role for drugs selective for these receptors is suggested by the critical pathophysiological roles of the human cell types (phagocytic leukocytes, vascular endothelial cells) known to express such receptors. The earlier, seminal work on the biologic actions of extracellular ATP was largely performed by smooth-muscle physiologists and pharmacologists. With the expanding range of, and interest in, this topic, recent studies have been carried out largely by diverse groups of pharmacologists, neurobiologists, physiologists, and biochemists. Not surprisingly, these various scientists often investigate certain aspects of extracellular ATP action from different perspectives, using the specialized tools and methods of their respective disciplines. Hopefully, by integrating these interdisciplinary perspectives on the biologic actions of extracellular ATP, there will be rapid progress in this field during the next few years.