title: Effect of ATP on Ca2+ uptake in the presence of high glucose in renal proximal tubule cells.
abstract: 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.
authors.affiliation: College of Veterinary Medicine, Biotechnology Research Institute, Chonnam National University, Gwangju 500-757, Korea. hjhan@chonnam.ac.kr
authors.forename: Ho Jae
authors.initials: HJ
authors.lastname: Han
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Park
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Lee
authors.forename: Jeong Chi
authors.initials: JC
authors.lastname: Lee
authors.forename: Jang Hern
authors.initials: JH
authors.lastname: Lee
mesh_terms: 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
chemical_list: D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D005947:Glucose; D002118:Calcium