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 language | English |
|---|---|
| Pages (from-to) | 383-386 |
| Number of pages | 4 |
| Journal | Biochemical Society Transactions |
| Volume | 32 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Apr 2004 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Phosphoinositide 3-kinase γ
T2 - Kinase-dependent and -independent activities in cardiovascular function and disease
AU - Alloatti, G.
AU - Montrucchio, G.
AU - Lembo, G.
AU - Hirsch, E.
PY - 2004/4
Y1 - 2004/4
N2 - 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.
AB - 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.
KW - β-adrenergic receptor
KW - Contractility
KW - G-protein-coupled receptor (GPCR)
KW - Heart disease
KW - Hypertrophy
KW - Phosphoinositide 3-kinase γ (PI3Kγ)
UR - http://www.scopus.com/inward/record.url?scp=2342537099&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=2342537099&partnerID=8YFLogxK
U2 - 10.1042/BST0320383
DO - 10.1042/BST0320383
M3 - Article
C2 - 15046613
AN - SCOPUS:2342537099
VL - 32
SP - 383
EP - 386
JO - Biochemical Society Transactions
JF - Biochemical Society Transactions
SN - 0300-5127
IS - 2
ER -