Adenosine and adenosine receptors in the pathomechanism and treatment of respiratory diseases.
It has been known for a long time that inhaled adenosine-monophosphate (AMP) induces airway obstruction in asthmatic patients, but not in healthy subjects. The mechanism of AMP is indirect and occurs via its decay product, adenosine. It stimulates mast cells through its low-affinity receptor A2B to release histamine, which ultimately leads to smooth muscle contraction. This feature of adenosine reveals its pro-inflammatory function, which may play important role in asthma. Indeed, mice lacking adenosine deaminase (ADA), an enzyme which decomposes adenosine, develop asthma-like disorder with elevated IgE, eosinophilia and airway hyperresponsiveness. Human studies showed elevated adenosine levels in bronchoalveolar lavage and exhaled breath condensate of asthmatics as compared to healthy people. Furthermore, certain human ADA phenotypes are associated with prevalence of asthma. These data suggest a protective role for ADA and a pro-inflammatory function for adenosine in asthma. The role of adenosine in inflammatory processes, however, is not unequivocal. Some in vitro studies showed that adenosine binding to its high-affinity receptor A2A results in inhibition of leukotriene synthesis or function of adhesion molecules. It is possible that the concentration of adenosine in lung tissues determines whether it promotes or reduces inflammation. Adenosine has also been associated with other respiratory diseases such as fibrosis, sarcoidosis, cystic fibrosis or tuberculosis. Identification of adenosine receptor subtypes and their role in the pathomechanism of respiratory diseases may provide new therapeutical targets. This review aims to summarize the role of adenosine and adenosine receptors in asthma and other pulmonary disorders.
Vass
G
G
Institute for Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest, Ullöi street 78/a, Hungary. hildiko@elet2.sote.hu
Horváth
I
I
D000241:Adenosine / Q000378:metabolism*; D000243:Adenosine Deaminase / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism*; D000402:Airway Obstruction / Q000378:metabolism; D000818:Animals; D006801:Humans; D008168:Lung / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D012140:Respiratory Tract Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*
D018047:Receptors, Purinergic P1; D000249:Adenosine Monophosphate; D000243:Adenosine Deaminase; D000241:Adenosine