Purine receptors in mammalian tissues: pharmacology and functional significance.

Abstract

Purine nucleosides and nucleotides are major factors in cell function. They are intermediates in energy pathways, in cellular metabolic processes and are constituents of the cofactors necessary for enzymatic reactions (1) and cell replication (2). It has therefore been difficult to visualize that such chemicals also act in cellular communication. The criteria used for evaluating whether a given compound is a neurotransmitter have been developed by historical precedent (3). They are based on knowledge of the prototypic neurotransmitter, acetylcholine (4). Adenosine has been identified as a neuromodulator using such classical criteria. This evaluation has lessened the enthusiasm for purine-related pro­ cesses as targets for therapeutic agents for malfunctions of mammalian homeostatis. There is no evidence that specific anabolic processes form adenosine, distinct from those involved in its general metabolic functions. Also, the physiological factors regulating the extracellular availability of the nucleoside and its distribution make the development of a purinergic hy­ pothesis of neuromodulation difficult (5). These issues are compounded by the paucity of dissimilar chemical entities that interact with adenosine recep­ tors. Agonists are almost exclusively purine nucleosides (6), whereas with few exceptions, most antagonists are imidazopyrimidines (7-10). Studies of adenosine receptor-mediated events are thus limited, comparable to in-