Adenosine modulates Mg2+ uptake in distal convoluted tubule cells via A1 and A2purinoceptors
| Autor: | Hyung Sub Kang, Dirk Kerstan, Gary A. Quamme, Long-Jun Dai, Gordon Ritchie |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
medicine.medical_specialty
Adenosine Physiology Distal tubule Mice Adenosine Triphosphate Internal medicine Phenethylamines Cyclic AMP Purinergic P1 Receptor Agonists medicine Animals Magnesium Distal convoluted tubule Enzyme Inhibitors Kidney Tubules Distal Aldosterone Protein Kinase Inhibitors Magnesium ion Cell Line Transformed Kidney Ion Transport Reabsorption Chemistry Receptors Purinergic P1 Cell biology medicine.anatomical_structure Endocrinology Purinergic P1 Receptor Antagonists Parathyroid Hormone Xanthines Theobromine Calcium medicine.drug |
| Zdroj: | American Journal of Physiology-Renal Physiology. 281:F1141-F1147 |
| ISSN: | 1522-1466 1931-857X |
| DOI: | 10.1152/ajprenal.2001.281.6.f1141 |
| Popis: | tk;1Adenosine plays a role in the control of water and electrolyte reabsorption in the distal tubule. As the distal convoluted tubule is important in the regulation of renal Mg2+ balance, we determined the effects of adenosine on cellular Mg2+ uptake in this segment. The effect of adenosine was studied on immortalized mouse distal convoluted tubule (MDCT) cells, a model of the intact distal convoluted tubule. The rate of Mg2+ uptake was measured with fluorescence techniques using mag-fura 2. To assess Mg2+ uptake, MDCT cells were first Mg2+ depleted to 0.22 ± 0.01 mM by being cultured in Mg2+-free media for 16 h and then placed in 1.5 mM MgCl2; next, changes in intracellular Mg2+ concentration ([Mg2+]i) were determined. [Mg2+]i returned to basal levels, 0.53 ± 0.02 mM, with a mean refill rate, d([Mg2+]i)/d t, of 137 ± 16 nM/s. Adenosine stimulates basal Mg2+ uptake by 41 ± 10%. The selective A1 purinoceptor agonist N 6-cyclopentyladenosine (CPA) increased intracellular Ca2+ and decreased parathyroid hormone (PTH)-stimulated cAMP formation and PTH-mediated Mg2+uptake. On the other hand, the selective A2 receptor agonist 2-[ p-(2-carbonyl-ethyl)-phenylethylamino]-5′- N-ethylcarboxamidoadenosine (CGS) stimulated Mg2+ entry in a concentration-dependent fashion. CGS increased cAMP formation and the protein kinase A inhibitor RpcAMPS inhibited CGS-stimulated Mg2+ uptake. Selective inhibition of phospholipase C, protein kinase C, or mitogen-activated protein kinase enzyme cascades with U-73122, Ro-31-8220, and PD-98059, respectively, diminished A2 agonist-mediated Mg2+ entry. Aldosterone potentiated CGS-mediated Mg2+ entry, and elevation of extracellular Ca2+ diminished CGS-responsive cAMP formation and Mg2+ uptake. Accordingly, MDCT cells possess both A1 and A2 purinoceptor subtypes with intracellular signaling typical of these respective receptors. We conclude that adenosine has dual effects on Mg2+ uptake in MDCT cells through separate A1 and A2purinoceptor pathways. |
| Databáze: | OpenAIRE |
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