ReviewAdenosine receptors as potential therapeutic targets
Section snippets
Inflammatory and immunological responses
Adenosine receptors play a modulatory role in inflammatory responses and there is increasing evidence for use of adenosine and its analogues in the treatment of severe inflammatory diseases such as arthritis5, 6 and asthma7, 8, 9, as well as for more general inflammatory processes such as wound healing10.
Cardiovascular system
Adenosine is effective as an antiarrhythmic agent in the treatment of tachycardia, or for unmasking atrial tachyarrhythmias or ventricular pre-excitation. By slowing down the electrical conductance in the sinus and atrioventricular nodes, adenosine slows down or terminates abnormal cardiac rhythms25, 26, 27. Because of the short half-life of adenosine, potentially serious side effects, such as atrial or ventricular fibrillation, apnea and acceleration of ventricular tachycardia, are usually
Renal system
Adenosine receptors are widely distributed throughout the nephron, mediating several effects in the renal system, therefore reducing the risk of cardiovascular disease in hypertensive patients45. Inhibition of adenosine deaminase has been shown to lower blood pressure in older but not younger spontaneous hypertensive rats. Hence, cardiovascular protection in older hypertensive patients might be achieved by using adenosine deaminase inhibitors45. Meanwhile, blockade of renal adenosine receptors
Parkinson’s disease
Several studies have recently suggested that the A2-receptor subtype is physiologically relevant in cerebral ischaemia54, neurological disorders55, 56 and neurodegenerative processes such as Parkinson’s disease54, 57, 58, 59.
The modulatory role of adenosine on dopamine and N-methyl-d-aspartate (NMDA)-receptor neurotransmission indicates a possible therapeutic potential for adenosine receptors in CNS disorders such as schizophrenia, dementia and depression (Fig. 3). Human studies with
Pain
Adenosine influences pain transmission both centrally and peripherally. In an inflammatory model of thermal hyperalgesia, spinally administered adenosine receptor agonists produce antinociception through the activation of A1 receptors74. The A1- and A2-receptor agonists, N6-cyclohexyladenosine (CHA) and CGS21680, and the adenosine kinase inhibitors, 5′-amino-5′deoxyadenosine (NH2dADO) and 5-iodotubercidin (ITU), produced antinociception in unilateral hind paw carrageenan-induced thermal
Conclusions
Adenosine receptors are widely distributed throughout the body. Recent studies demonstrate that adenosine receptors are involved in complex regulatory systems. A clear understanding of the specific interactions in the cardiovascular, respiratory, renal, central and peripheral nervous systems and in immunological and inflammatory processes are likely to lead to new approaches for the use of adenosine receptor agonists and antagonists in a wide range of diseases.
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