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Dissecting the regulatory mechanisms controlling inhibitory adenosine receptor signaling
Author(s) -
Palmer Timothy M.,
Ferguson Gail,
Watterson Kenneth R.
Publication year - 2003
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.10185
Subject(s) - adenosine , adenosine a2b receptor , adenosine a3 receptor , adenosine receptor , g protein coupled receptor , receptor , purinergic signalling , agonist , biology , molecular pharmacology , extracellular , microbiology and biotechnology , signal transduction , pharmacology , adenosine a1 receptor , chemistry , biochemistry
The ability of target cells to respond to rapid changes in extracellular adenosine concentrations that occur in response to ischemia is determined by their complement of adenosine receptors. Four adenosine receptor subtypes, termed A 1 , A 2A , A 2B , and A 3 , have been identified by pharmacological and molecular cloning studies. In addition to displaying distinct pharmacological characteristics, each receptor mediates its intracellular effects by coupling to defined G‐protein families. Our studies have concentrated on applying a combination of molecular biological, biochemical, and cell biological approaches to define the molecular mechanisms by which adenosine receptor‐derived signaling events are regulated. These studies have revealed that the desensitization of closely related adenosine receptors, which bind the same agonist in vivo (i.e., adenosine) and activate the same family of G proteins, is mediated by unique receptor‐specific mechanisms. In this review, the nature of these differences, and how they could potentially be exploited to test novel strategies for enhancing the cardioprotective effects of inhibitory adenosine receptor activation in vivo, will be described. Drug Dev. Res. 58:302–314, 2003. © 2003 Wiley‐Liss, Inc.