Blackwell Publishing Journal Backfiles 1879-2005
1. Calcium regulation has been reported to be associated with the development of diabetic nephropathy. Thus, changes in Ca2+ uptake induced by ATP, an important regulator of Ca2+ 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 Ca2+ uptake early on (〈 30 min), whereas Ca2+ 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 Ca2+.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 Ca2+ uptake in the presence of 25 mmol/L glucose. However, none one of these drugs blocked the effect of ATP on Ca2+ 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 Ca2+ uptake via cAMP and PKC pathways in the PTC.
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