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Coordinate adenosine A 1 and A 2A receptors regulation of the Na + /H + exchanger 3 in ischemia/reperfusion injury
Author(s) -
Babich Victor,
Vadnagara Komal,
Moe Orson W,
Di Sole Francesca
Publication year - 2012
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.26.1_supplement.1152.20
Subject(s) - agonist , chemistry , sodium–hydrogen antiporter , reperfusion injury , adenosine a1 receptor , ischemia , receptor , adenosine , pharmacology , endocrinology , medicine , adenosine receptor , biochemistry , organic chemistry , sodium
Acute kidney injury, due to ischemia/reperfusion injury (IRI), is associated with high morbidity and mortality and lacks specific therapeutic measures. Na + absorption is severely compromised by IRI and both surface and total protein of the principal proximal tubule Na + transporter, the Na + /H + exchanger 3 (NHE3), are markedly decreased following IRI. We found that coordinate pharmacological activation of adenosine receptor subtype 1 (A1R) and 2A (A2AR) protected against IRI. Compared to vehicle‐treated ischemic rats, A1R agonist, given before ischemia, and A2AR agonist, given after ischemia, decreased the peak of plasma creatinine (Cr) and blood urea nitrogen (BUN) 24 hours after IRI and accelerated their reversal thereafter. We next examined how A1R and A2AR affect NHE3 protein expression in IRI. A1R agonist, given before ischemia, did not affect the drop in NHE3 surface, but blunted IRI‐induced reduction in NHE3 total protein. A2AR agonist, given after ischemia, reversed the decrease in NHE3 surface but did not affect loss of NHE3 total protein mediated by IRI. In summary, activation of A1R and A2AR synergistically reduced the peak and accelerated the reversal of Cr and BUN following IRI. A1R and A2AR act differently, but in conjunction, to preserve NHE3 protein and move it back to cell surface after IRI. Modulation of NHE3 protein expression may be a key mechanism by which A1R and A2AR mediate protection against IRI.