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Effect of ATP on Ca 2+ uptake in the presence of high glucose in renal proximal tubule cells
Author(s) -
Han Ho Jae,
Park Soo Hyun,
Lee Yun Jung,
Lee Jeong Chi,
Lee Jang Hern
Publication year - 2003
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2003.03895.x
Subject(s) - protein kinase c , staurosporine , endocrinology , medicine , adenylate kinase , chemistry , bisindolylmaleimide , glucose uptake , calcium , biochemistry , enzyme , biology , insulin
Summary 1. Calcium regulation has been reported to be associated with the development of diabetic nephropathy. Thus, changes in Ca 2+ uptake induced by ATP, an important regulator of Ca 2+ uptake, in the diabetic condition and related signal pathways were examined in primary cultures of rabbit renal proximal tubule cells (PTC). 2. Under low (5 mmol/L) glucose conditions, 10 −4 mol/L ATP inhibited Ca 2+ uptake early on (< 30 min), whereas Ca 2+ uptake was stimulated at later time points (> 2 h). However, under high (25 mmol/L) glucose conditions, ATP stimulated both the early and late uptake of Ca 2+ . 3. The adenylate cyclase inhibitor SQ 22536, the protein kinase (PK) A inhibitor PKI amide 14–22, Rp‐cAMP, staurosporine, bisindolylmaleimide I and H‐7 (PKC inhibitors) blocked the change in ATP effect on Ca 2+ uptake in the presence of 25 mmol/L glucose. However, none one of these drugs blocked the effect of ATP on Ca 2+ uptake in the presence of 5 mmol/L. 4. At 25 mmol/L, glucose increased cAMP content and PKC activity, whereas ATP had no effect on either parameter. 5. In conclusion, high glucose levels alter ATP‐induced Ca 2+ uptake via cAMP and PKC pathways in the PTC.