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Short‐ and long‐term A~3~ adenosine receptor activation inhibits the Na^+^/H^+^ exchanger NHE3 activity and expression in opossum kidney cells by Francesca Di Sole; Robert Cerull; Victor Babich; Valeria Casavola; Corinna Helmle-Roth; Gerhard Burckhardt is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
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## Abstract The renal function of the A~3~ adenosine receptor (A3AR) is poorly characterized. In this study, we report that the A3AR‐selective agonist, 1‐[2‐chloro‐6‐[[(3‐iodophenyl)methyl]amino]‐9__H__‐purine‐9‐yl]‐1‐deoxy‐__N__‐methyl‐b‐D‐ribofuranuronamide (2‐Cl‐IBMECA) regulates the Na^+^/H^+^ exchanger‐3 (NHE3) in a dose‐ and time‐dependent fashion. In opossum kidney (OK) cells, 2‐Cl‐IBMECA at high (10^−6^ M) and low (10^−8^ M) dose inhibits NHE3 by a multiphasic time course with an acute phase of NHE3 inhibition from 15 min to 1 h, followed by a chronic phase of NHE3 inhibition from 24 to 48 h. Pre‐incubation with either the selective A3AR‐antagonist MRS1523 (10^−7^ M) or the protein kinase C inhibitor, Calphostin C (10^−8^ M) completely blocked 10^−6^ M 2‐Cl‐IBMECA‐induced acute (15 min) and chronic (24 h) phases of NHE3 inhibition. In contrast, the acute inhibitory phase (15 min) of 10^−8^ M 2‐Cl‐IBMECA was completely prevented only when Calphostin C (10^−8^ M) was added in conjunction with the protein kinase A inhibitor, H89 (10^−7^ M). Acute (15 or 30 min depending on the A3AR‐agonist concentration) A3AR‐dependent inhibition of NHE3 activity was accompanied by decrease in
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- Author
- Francesca Di Sole; Robert Cerull; Victor Babich; Valeria Casavola; Corinna Helmle-Roth; Gerhard Burckhardt
- Publisher
- John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley (ISSN 0021-9541)
- Published
- 2008
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)