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Evidence of crosstalk between A 1 and A 2A adenosine receptor in the regulation of renal O 2 consumption
Author(s) -
Di Sole Francesca,
Babich Victor,
Moe Orson W
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1059.12
Subject(s) - adenosine , agonist , chemistry , adenosine deaminase , endogeny , medicine , endocrinology , receptor , adenosine receptor , antagonist , kidney , biology , biochemistry
Limited O 2 availability leads to high level of adenosine which protects the kidney via both A 1 and A 2A adenosine receptor (A 1 R and A 2A R). Relative contribution of A 1 R and A 2A R is not clear. We evaluated the effect of acute A 1 R and A 2A R activation on the rate of O 2 consumption (VO 2 ) in renal cortex which has high O 2 requirement. A 1 R agonist, CPA, and A 2A agonist, CGS, both inhibited VO 2 in a dose and time dependent mode. Reduction in VO 2 was Na + dependent for A 1 R and Na + independent for A 2A , suggesting the two receptors act differently to reduce VO 2 . To eliminate endogenous adenosine, we metabolized it by incubation with adenosine deaminase (ADA). We found a strong reduction in VO 2 that was Na + dependent. Likewise, A 1 R antagonist, CPX, also reduced VO 2 . This data suggests that in contradistinction to exogenously added A 1 R agonist, endogenous adenosine increases VO 2 via A 1 R. Furthermore, in ADA pretreated tissue, we found that: 1. A 1 R has dual mode of action. Low dose of CPA activates and high dose inhibits VO 2 and both effects were Na + dependent. 2. CGS has no effect on the reduction in VO 2 induced by ADA but converted the Na + dependent A 1 R mediated effect on VO 2 to a mainly Na + independent effect. In summary, A 1 R affects VO 2 via Na + dependent, while A 2A R via Na + independent mechanisms. If both A 1 R and A 2A R are activated Na + independent mechanisms prevails on the Na + dependent mechanisms suggesting crosstalk between A 1 R and A 2A R. These findings indicate that increasing level of adenosine decreases VO 2 via both Na + dependent and independent mechanisms depending on the receptor subtype activated and the two mechanisms are interdependent.