title: Dual signaling via protein kinase C and phosphatidylinositol 3'-kinase/Akt contributes to bradykinin B2 receptor-induced cardioprotection in guinea pig hearts.
abstract: We investigated the role of protein kinase C (PKC) and phosphatidylinositol 3;-kinase (PI3-K) in the signaling mechanism of cardioprotection afforded by bradykinin (BK). Coronary-perfused guinea pig ventricular muscles were subjected to 20-min no-flow ischemia and 60-min reperfusion. Pretreatment for 5 min with BK (1 microm) significantly improved the recovery of developed tension measured after 60 min of reperfusion (86.8+/-2.6%v 34.8+/-4.1% in control). Prior treatment with B2 receptor antagonist HOE 140 completely abolished the protective effect of BK (37.0+/-7.6%). The protection was reduced by either PKC inhibitor chelerythrine (CH, 58.9+/-2.2%) or PI3-K inhibitor wortmannin (WM, 59.4+/-2.5%); however, the recovery of contractility was intermediate between the BK and control groups. Nevertheless, pretreatment with CH and WM together completely eliminated the protective effect of BK (38.9+/-4.2%). The mitochondrial ATP-sensitive K+ (mitoK(ATP)) channel blocker 5-hydroxydecanoate (5HD) significantly but partially inhibited the effect of BK (59.0+/-2.2%). Pretreatment with 5HD and CH together could not generate further inhibition (61.1+/-3.3%), while pretreatment with 5HD and WM together totally eliminated the protection (34.9+/-2.9%). We conclude that BK B2 receptors can precondition guinea pig hearts via the dual activation of PKC and PI3-K. The mitoK(ATP) channels act as downstream targets of PKC, whereas PI3-K is not associated with mitoK(ATP) channels.
authors.affiliation: Department of Physiology, Oita Medical University, Oita, 879-5593, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: T
authors.initials: T
authors.lastname: Sato
mesh_terms: D000470:Alkaloids; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D053119:Benzophenanthridines; D015153:Blotting, Western; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D003652:Decanoic Acids / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006880:Hydroxy Acids / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010617:Phenanthridines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000378:metabolism; D015424:Reperfusion; D015427:Reperfusion Injury; D015398:Signal Transduction; D044005:Tetrahydroisoquinolines; D013997:Time Factors
chemical_list: D000470:Alkaloids; D000889:Anti-Arrhythmia Agents; D053119:Benzophenanthridines; D001920:Bradykinin; D003652:Decanoic Acids; D004791:Enzyme Inhibitors; D006880:Hydroxy Acids; D010617:Phenanthridines; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D044005:Tetrahydroisoquinolines; C078665:HOE 140, desArg(10)-; C052853:5-hydroxydecanoic acid; C016299:chelerythrine