XXXX effect on phospholipid synthesis in ventricular myocytes: consequences in alpha-adrenergic signaling.

@entity8580 @entity35 @entity6546 @entity1184 @entity2647 @entity1481 @entity2904 @entity4113 @entity4357
The anti-anginal drug @entity1481 ( @entity2904 ) has been shown to increase the synthesis of phospholipids in ventricular myocytes, including @entity4357 (PI). This study focused on the consequences of increasing PI metabolism on alpha-adrenergic signaling pathway in cultured @entity35 cardiomyocytes. In the cells treated with @entity2904 , the synthesis of PI from @entity8580 was largely increased as compared with the control (+55% in 60 min). The stimulation of alpha-adrenergic receptors by @entity2647 (PE) induced a dose-dependent production of inositide @entity6546 (IPs) by phospholipase C (PLC) activation. However, the amount of available IPs was significantly lower in @entity2904 -treated cells, in a dose-dependent manner. This effect was observed in the presence and absence of the IP1-phosphatase inhibitor @entity4113 . The in vitro determination of PLC activity revealed that this effect could not be attributed to the direct inhibition of the enzyme by @entity2904 . The @entity2904 -induced reduction of IPs in the PE-stimulated cardiomyocytes should be attributed to the increase of @entity8580 recycling and incorporation in membrane structures, elicited by increased phospholipid synthesis. The consequences of this reduction in IPs availability were investigated on the cardiomyocyte @entity1184 induced by alpha-adrenergic chronic stimulation. Acute stimulation with PE increased protein synthesis (+50%), but this increase was largely prevented by @entity2904 . In conclusion, @entity2904 reduces cell available IPs, by accelerating their recycling in membranes as PI. This effect results in a cytoprotection in the pathological process of @entity1184 elicited by chronic alpha-adrenergic stimulation.
