New insights into the molecular mechanisms of A1 adenosine receptor action

A(1) adenosine receptors (A(1)ARs) mediate the effects of adenosine in many tissues, making this receptor subtype an extremely important transducer of adenosine action. Recent structure-function and computer modeling studies based on the structure of mammalian rhodopsin suggest that the upper part of the purine ring and the N-6-substituent of adenosine interact with Thr91 and Gln92 in TM3, and the ribose moiety interacts with Thr277 and His278 in TM7, and Ser94 in TM3. When contemporary methods are applied to examine sites of A(1)AR expression in the brain, axons are now found to express A(1)ARs at very high levels, and functional studies show that adenosine can influence mammalian nerve conduction. A(1)ARs are expressed in the brain and heart at early embryonic stages, raising the intriguing possibility that adenosine exerts important effects during development, and adenosine may be one of the most potent regulators of embryonic cardiac function. These observations provide new insights into the sites and mechanisms of A(1)AR action. Drug Dev. Res. 45:93-102, 1998. (C) 1998 Wiley-Liss, Inc.