Dual signaling via protein kinase C and phosphatidylinositol 3′-kinase/Akt contributes to bradykinin B2 receptor-induced cardioprotection in guinea pig hearts

Yulong Li, Toshiaki Sato

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Y. Li and T. Sato. Dual Signaling via Protein Kinase C and Phosphatidylinositol 3′-Kinase/Akt Contributes to Bradykinin B2 Receptor-induced Cardioprotection in Guinea Pig Hearts. Journal of Molecular and Cellular Cardiology (2001) 33, 2047-2053. 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 μM) 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+ (mitoKATP) 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 mitoKATP channels act as downstream targets of PKC, whereas PI3-K is not associated with mitoKATP channels.

Original languageEnglish (US)
Pages (from-to)2047-2053
Number of pages7
JournalJournal of Molecular and Cellular Cardiology
Volume33
Issue number11
DOIs
StatePublished - Jan 1 2001

Keywords

  • Bradykinin
  • Phosphatidylinositol 3′-kinase
  • Preconditioning
  • Protein kinase C

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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