Phosphoinositide 3-kinase γ: Kinase-dependent and -independent activities in cardiovascular function and disease

G. Alloatti, G. Montrucchio, G. Lembo, E. Hirsch

Research output: Contribution to journalArticle

Abstract

Cardiac function is controlled by GPCRs (G-protein-coupled receptors) which exert their function by triggering numerous signalling pathways, including the activation of PI3K (phosphoinositide 3-kinase). The GPCR-activated PI3Kγ is weakly expressed in the heart, but the deletion of its expression in mice causes remarkable phenotypes. Indeed, the lack of PI3Kγ does not modify heart rate and blood pressure, but does increase contractility, particularly in response to stimuli that enhance cardiac contractile force, such as catecholamines. Consistently, treatment of mutant cardiomyocytes with β-adrenergic agonists causes an abnormal increase in the elevation of cAMP production. On the other hand, PI3Kγ appears to play a role in mediating the contractile depression exerted by other GPCR agonists, such as PAF (platelet-activating factor), that are released in pathological conditions, such as after an ischaemic insult. The receptor for PAF coupled to Gi activates PI3Kγ, which, in turn, is essential to promote Akt phosphorylation, NOSIII (nitric oxide synthase isoform III) activation and the production of nitric oxide, a well characterized cardiodepressing agent. As a whole, PI3Kγ appears to negatively control cardiac contractility through different signalling mechanisms, thus becoming a possible drug target for the treatment of critical human cardiac pathologies, such as infarction or heart failure.

Original languageEnglish
Pages (from-to)383-386
Number of pages4
JournalBiochemical Society Transactions
Volume32
Issue number2
DOIs
Publication statusPublished - Apr 2004

Fingerprint

1-Phosphatidylinositol 4-Kinase
Phosphatidylinositols
Cardiovascular Diseases
Phosphotransferases
G-Protein-Coupled Receptors
Chemical activation
Adrenergic Agonists
Phosphorylation
Platelet Activating Factor
Blood pressure
Pathology
Cardiac Myocytes
Nitric Oxide Synthase
Infarction
Catecholamines
Nitric Oxide
Protein Isoforms
Heart Failure
Heart Rate
Blood Pressure

Keywords

  • β-adrenergic receptor
  • Contractility
  • G-protein-coupled receptor (GPCR)
  • Heart disease
  • Hypertrophy
  • Phosphoinositide 3-kinase γ (PI3Kγ)

ASJC Scopus subject areas

  • Biochemistry

Cite this

Phosphoinositide 3-kinase γ : Kinase-dependent and -independent activities in cardiovascular function and disease. / Alloatti, G.; Montrucchio, G.; Lembo, G.; Hirsch, E.

In: Biochemical Society Transactions, Vol. 32, No. 2, 04.2004, p. 383-386.

Research output: Contribution to journalArticle

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