The β2-adrenergic receptor delivers an antiapoptotic signal to cardiac myocytes through G(i)-dependent coupling to phosphatidylinositol 3'-kinase

Alan Chesley, Martha S. Lundberg, Toshinobu Asai, Rui Ping Xiao, Seiji Ohtani, Edward G. Lakatta, Michael T. Crow

Research output: Contribution to journalArticle

Abstract

Recent studies have shown that chronic β-adrenergic receptor (β-AR) stimulation alters cardiac myocyte survival in a receptor subtype-specific manner. We examined the effect of selective β1- and β2-AR subtype stimulation on apoptosis induced by hypoxia or H2O2 in rat neonatal cardiac myocytes. Although neither β1- nor β2-AR stimulation had any significant effect on the basal level of apoptosis, selective β2-AR stimulation protected myocytes from apoptosis. β2-AR stimulation markedly increased mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) activation as well as phosphatidylinositol-3'-kinase (PI-3K) activity and Akt/protein kinase B phosphorylation. β1-AR stimulation also markedly increased MAPK/ERK activation but only minimally activated PI-3K and Akt. Pretreatment with pertussis toxin blocked β2-AR-mediated protection from apoptosis as well as the β2-AR-stimulated changes in MAPK/ERK, PI-3K, and Akt/protein kinase B. The selective PI-3K inhibitor, LY 294002, also blocked β2-AR-mediated protection, whereas inhibition of MAPK/ERK activation at an inhibitor concentration that blocked agonist-induced activation but not the basal level of activation had no effect on β2-AR-mediated protection. These findings demonstrate that β2-ARs activate a PI-3K-dependent, pertussis toxin-sensitive signaling pathway in cardiac myocytes that is required for protection from apoptosis-inducing stimuli often associated with ischemic stress.

Original languageEnglish (US)
Pages (from-to)1172-1179
Number of pages8
JournalCirculation research
Volume87
Issue number12
DOIs
StatePublished - Dec 8 2000

Keywords

  • Apoptosis
  • Cardiomyocytes
  • G proteins
  • Hypoxia
  • Phosphatidylinositol 3'-kinase
  • β-adrenergic receptors

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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