Adenosine and Adenosine Receptors

Historically, the major emphasis on the study of purinergic systems has been predominantly in the areas of physiology and gross pharmacology. The last decade has seen an exponential in crease in the number of publications related to the role of both adenosine and A TP in mammalian tissue function, a level of interest that has evolved from a more molecular focus on the identity of adenosine and A TP receptor subtypes and the search for selective ligands and development of radioligand binding assays by Fred Bruns and colleagues (especially that for A receptors) that played z a highly significant role in advancing research in the area. In the 60 years since adenosine was first shown to be a potent hypotensive agent, a considerable investment has been made by several pharmaceutical companies-including Abbott, Byk Gulden, Takeda, Warner-LambertlParke Davis, Boehringer Mann heim, Boehringer Ingelheim, Nelson/Whitby Research and CffiA Geigy-as well as John Daly's laboratory at the National Institutes of Health, to design new adenosine receptor ligands, and both agon ists and antagonists with the aim of developing new therapeutic entiities. Numerous research tools have derived from these efforts including: 2-chloroadenosine, R-PIA (~-phenylisopropyladeno sine; NECA (5' N-ethylcarboxamidoadenosine); CV1808; CI936; PD 125,944; ~-benzyladenosine; PACPX; CPX; CPT; XAC; CGS 15943 and CGS 21680. Yet in the realm of therapeutics it was only in 1989 that adenosine itself was approved for human use in the treatment of supraventricular arrythmias.

Section I: Historical Perspective.- 1 Adenosine Receptors: An Historical Perspective.- Section 2: Characterization of the Receptor and Its Binding Site.- 2 Radioligand Binding Assays for Adenosine Receptors.- 3 Structure-Activity Relationships of Adenosine A1 and A2 Receptors.- Section 3: Biochemical Mechanisms of Receptor Action.- 4 Signal Transduction Mechanisms for Adenosine.- 5 Electrophysiological Aspects of Adenosine Receptor Function.- 6 Adenosine Release.- 7 Adenosine Deaminase and [3H]Nitrobenzylthionosine as Markers of Adenosine Metabolism and Transport in Central Purinergic Systems.- Section 4: Physiological Functions of Adenosine Receptors.- 8 Adenosine and Cardiovascular Function.- 9 Adenosine and Renal Function.- 10 The Role of Adenosine in Respiratory Physiology.- 11 Adenosine in Central Nervous System Function.- Section 5: Receptor Regulation.- 12 Adenosine and Host Defense: Modulation Through Metabolism and Receptor-Mediated Mechanisms.- Section 6: Future Vistas.- 13 Adenosine Receptors: Future Vistas.