title: Role of intracellular Ca2+ in activation of protein kinase C during ischemic preconditioning.
abstract: BACKGROUND
  Activation of protein kinase C plays an important role in ischemic preconditioning. Given that protein kinase C is activated by an increase in the intracellular Ca2+ concentration ([Ca2+]i) and that myocardial ischemia and reperfusion increase [Ca2+]i, the effect of transient exposures to Ca2+ on infarct size and the effect of administration of EGTA during ischemic and alpha1-adrenoceptor-mediated preconditioning on the limitation of infarct size were investigated in the canine heart.
  
  
  RESULTS
  In open-chest dogs, 5 minutes after the completion of either three 5-minute infusions of CaCl2 or four 5-minute infusions of the alpha1-adrenoceptor agonist methoxamine into the coronary artery, the coronary arteries were occluded for 90 minutes; this occlusion was followed by a 6-hour reperfusion in both the Ca2+ preconditioning and methoxamine groups. Infarct sizes in the Ca2+ preconditioning (15.8+/-2.3%) and methoxamine (10.1+/-2.2%) groups were significantly (P<.01) smaller than in the control group (42.5+/-2.9%), and administration of either an inhibitor of protein kinase C (GF109203X) or an inhibitor of ecto-5'-nucleotidase (alpha,beta-methyleneadenosine 5'-diphosphate) reduced the infarct size-limiting effect of Ca2+ preconditioning. Administration of EGTA during ischemic or alpha1-adrenoceptor-mediated preconditioning inhibited both the infarct size-limiting effect and the activation of protein kinase C and ecto-5'-nucleotidase induced by these procedures.
  
  
  CONCLUSIONS
  [Ca2+]i during ischemic and alpha1-adrenoceptor-mediated preconditioning plays an important role in the infarct size-limiting effect of these procedures by activating protein kinase C and ecto-5'-nucleotidase in the canine heart.
authors.affiliation: First Department of Medicine, Osaka University School of Medicine, Suita, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Node
authors.forename: M
authors.initials: M
authors.lastname: Kitakaze
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Minamino
authors.forename: K
authors.initials: K
authors.lastname: Komamura
authors.forename: Y
authors.initials: Y
authors.lastname: Shinozaki
authors.forename: H
authors.initials: H
authors.lastname: Mori
authors.forename: M
authors.initials: M
authors.lastname: Hori
mesh_terms: D015720:5'-Nucleotidase / Q000187:drug effects; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002122:Calcium Chloride / Q000494:pharmacology*; D004285:Dogs; D004533:Egtazic Acid / Q000494:pharmacology; D004699:Endocardium / Q000473:pathology; D019157:Ischemic Preconditioning, Myocardial; D008729:Methoxamine / Q000494:pharmacology; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D011493:Protein Kinase C / Q000378:metabolism*
chemical_list: D000316:Adrenergic alpha-Agonists; D004533:Egtazic Acid; D011493:Protein Kinase C; D015720:5'-Nucleotidase; D008729:Methoxamine; D002122:Calcium Chloride; D002118:Calcium