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.
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April 2004
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Conference Article|
April 01 2004
Phosphoinositide 3-kinase γ: kinase-dependent and -independent activities in cardiovascular function and disease
G. Alloatti;
G. Alloatti
*Dipartimento di Biologia Animale e dell'Uomo e Istituto Nazionale per la Fisica della Materia, Università di Torino, Torino, Italy
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G. Montrucchio;
G. Montrucchio
†Dipartimento di Fisiopatologia Clinica, Università di Torino, Torino, Italy
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G. Lembo;
G. Lembo
‡I.R.C.C.S. Neuromed, Pozzilli (Isernia), Italy
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E. Hirsch
E. Hirsch
1
§Dipartimento di Genetica, Biologia e Biochimica, Università di Torino, Torino, Italy
1To whom correspondence should be addressed (e-mail emilio.hirsch@unito.it).
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Publisher: Portland Press Ltd
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2004 Biochemical Society
2004
Biochem Soc Trans (2004) 32 (2): 383–386.
Citation
G. Alloatti, G. Montrucchio, G. Lembo, E. Hirsch; Phosphoinositide 3-kinase γ: kinase-dependent and -independent activities in cardiovascular function and disease. Biochem Soc Trans 1 April 2004; 32 (2): 383–386. doi: https://doi.org/10.1042/bst0320383
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