title: Purinergic P2X7 receptors participate in disturbed intracellular calcium homeostasis in peripheral blood mononuclear cells of patients with chronic kidney disease.
abstract: BACKGROUND
  P2X(7) receptors intervene with lymphocyte activation and are responsible for multiple processes, including calcium influx. Here, we studied the participation of P2X(7) receptors in disturbed intracellular calcium homeostasis regulation in early-stage chronic kidney disease (CKD).
  
  
  METHODS
  The study involved 20 healthy volunteers and 20 CKD stage 2-3 patients. The free cytosolic calcium concentration ([Ca(2+)](i)) was measured using fluorimetry. The P2X(7) pore function was evaluated by the fluorescent dye ethidium bromide.
  
  
  RESULTS
  In peripheral blood mononuclear cells (PBMCs) of patients, [Ca(2+)](i), intracellular calcium stores and the capacitative calcium entry were increased when compared with healthy subjects. The agonist of P2X(7) receptor BzATP caused a sustained increase in [Ca(2+)](i) in both groups, but the effect was smaller in patients. The antagonist at the P2X(7) receptor KN-62 reduced [Ca(2+)](i) in patients, but had no effect in healthy subjects. In patients, the permeability of ethidium bromide through P2X(7) pores, as well as through BzATP-activated and KN-62-inhibited pores, was distinct from permeability in healthy volunteers.
  
  
  CONCLUSIONS
  These results demonstrate that the calcium signaling pathway in PBMCs of CKD patients is defective already in CKD stage 2-3, and the pore-forming P2X(7) receptors are involved in these pathophysiological processes.
authors.affiliation: Department of Clinical and Experimental Pharmacology, Faculty of Medicine, Slovak Medical University, Bratislava, Slovak Republic. ingrid.lajdova@szu.sk
authors.forename: Ingrid
authors.initials: I
authors.lastname: Lajdova
authors.forename: Adrian
authors.initials: A
authors.lastname: Oksa
authors.forename: Dusan
authors.initials: D
authors.lastname: Chorvat
authors.forename: Peter
authors.initials: P
authors.lastname: Topor
authors.forename: Viera
authors.initials: V
authors.lastname: Spustova
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000328:Adult; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006706:Homeostasis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058486:Receptors, Purinergic P2X7 / Q000502:physiology*; D051436:Renal Insufficiency, Chronic / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*
chemical_list: D058486:Receptors, Purinergic P2X7; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000255:Adenosine Triphosphate