Effect of ATP on Ca2+ uptake in the presence of high glucose in renal proximal tubule cells.
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.
Han
Ho Jae
HJ
College of Veterinary Medicine, Biotechnology Research Institute, Chonnam National University, Gwangju 500-757, Korea. hjhan@chonnam.ac.kr
Park
Soo Hyun
SH
Lee
Yun Jung
YJ
Lee
Jeong Chi
JC
Lee
Jang Hern
JH
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D011817:Rabbits
D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D005947:Glucose; D002118:Calcium