Abstract |
A(3) adenosine receptor (AR) activation and inhibition worsen and improve, respectively, renal function after ischemia-reperfusion (I/R) injury in rats. We sought to further characterize the role of A(3) ARs in modulating renal function after either I/R or myoglobinuric renal injury. A(3) knockout mice had significantly lower plasma creatinines compared with C57 controls 24 h after I/R or myoglobinuric renal injury. C57 control mice pretreated with the A(3) AR antagonist [3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(+/-)- dihydropyridine-3,5 dicarboxylate] or agonist [0.125 mg/kg N(6)-(3-iodobenzyl)-N-methyl-5'-carbamoyladenosine ( IB-MECA)] demonstrated improved or worsened renal function, respectively, after I/R or myoglobinuric renal injury. Higher doses of IB-MECA were lethal in C57 mice subjected to renal ischemia. H(1) but not H(2) histamine receptor antagonist prevented death in mice pretreated with IB-MECA before renal ischemia. Improvement in renal function was associated with significantly improved renal histology. In conclusion, preischemic A(3) AR activation (0.125 mg/kg IB-MECA) exacerbated renal I/R injury in mice. Mice lacking A(3) ARs or blocking A(3) ARs in wild-type mice resulted in significant renal protection from ischemic or myoglobinuric renal failure.
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Authors | H Thomas Lee, Ayuko Ota-Setlik, Hua Xu, Vivette D D'Agati, Marlene A Jacobson, Charles W Emala |
Journal | American journal of physiology. Renal physiology
(Am J Physiol Renal Physiol)
Vol. 284
Issue 2
Pg. F267-73
(Feb 2003)
ISSN: 1931-857X [Print] United States |
PMID | 12388399
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Purinergic P1 Receptor Agonists
- Receptor, Adenosine A3
- Receptors, Purinergic P1
- N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine
- p-Methoxy-N-methylphenethylamine
- Histamine
- Adenosine
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Topics |
- Acute Kidney Injury
(pathology, physiopathology, prevention & control)
- Adenosine
(analogs & derivatives, pharmacology, toxicity)
- Animals
- Genotype
- Histamine
(blood)
- Ischemia
(metabolism, pathology, physiopathology)
- Kidney
(pathology, physiopathology)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
(genetics)
- Myoglobinuria
(metabolism, physiopathology)
- Purinergic P1 Receptor Agonists
- Receptor, Adenosine A3
- Receptors, Purinergic P1
(drug effects)
- Reference Values
- Renal Circulation
- Reperfusion Injury
(metabolism, pathology)
- p-Methoxy-N-methylphenethylamine
(pharmacology, toxicity)
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