title: Molecular basis of P2-receptor-mediated calcium signaling in activated pancreatic stellate cells.
abstract: OBJECTIVE
  There is growing evidence that extracellular nucleotide-induced signaling confers to fibrogenesis in liver and pancreas. Pancreatic stellate cells (PSC) are the most important cell type in pancreatic fibrosis. P2 purine and pyrimidine receptors, again, are pivotal mediators of inflammatory and profibrogenic signals. Our aim was to elucidate the underlying signaling components in activated PSC.
  
  
  METHODS
  We performed expression analysis of calcium ion (Ca(2+)) signaling components and monitored real-time intracellular Ca(2+) responses to nucleotides in rat PSC.
  
  
  RESULTS
  Adenosine monophosphate, adenosine diphosphate, and adenosine-5'-triphosphate elicited detectable rises in intracellular Ca(2+) concentrations. Stimulation of PSC by ATP led to intracellular Ca signals mediated through both P2X and P2Y receptors. Whereas uridine triphosphate-mediated Ca(2+) signals were generated by activation of P2Y receptors only, uridine diphosphate stimulated P2X receptors as well. Of the phospholipase C (PLC)/inositol-1,4,5-trisphosphate pathway, all PLC-facilitating Gα subunits were present in activated cells as were all 3 inositol-1,4,5-trisphosphate receptor isoforms. In addition, transcripts of PLC-β and PLC-δ isoforms were also strongly detectable.
  
  
  CONCLUSIONS
  Activated PSC feature a plethora of elements from the Ca signaling toolkit and functionally express a subset of P2 nucleotide receptors. Purines and pyrimidines elicit robust intracellular Ca(2+) signals likely contributing to the fibrogenetic potential of these cells.
authors.affiliation: Department of Internal Medicine II-Oncology, Hematology, BMT with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jan K
authors.initials: JK
authors.lastname: Hennigs
authors.forename: Oliver
authors.initials: O
authors.lastname: Seiz
authors.forename: Julia
authors.initials: J
authors.lastname: Spiro
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Berna
authors.forename: Hans Jörg
authors.initials: HJ
authors.lastname: Baumann
authors.forename: Hans
authors.initials: H
authors.lastname: Klose
authors.forename: Andrea
authors.initials: A
authors.lastname: Pace
mesh_terms: D000818:Animals; D001483:Base Sequence; D020013:Calcium Signaling / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D005355:Fibrosis; D020869:Gene Expression Profiling; D008297:Male; D008954:Models, Biological; D058954:Pancreatic Stellate Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011685:Purine Nucleotides / Q000494:pharmacology; D011742:Pyrimidine Nucleotides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D058848:Receptors, Purinergic P2X4 / Q000235:genetics / Q000378:metabolism; D058473:Receptors, Purinergic P2Y2 / Q000235:genetics / Q000378:metabolism
chemical_list: D017931:DNA Primers; D011685:Purine Nucleotides; D011742:Pyrimidine Nucleotides; D018048:Receptors, Purinergic P2; D058848:Receptors, Purinergic P2X4; D058473:Receptors, Purinergic P2Y2