| Autor: |
Tappia PS; Asper Clinical Research Institute, St. Boniface Hospital, Winnipeg, R2H 2A6 MB Canada., Ramjiawan B; Asper Clinical Research Institute, St. Boniface Hospital, Winnipeg, R2H 2A6 MB Canada.; Department of Pharmacology and Therapeutics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, R3E 0T6 MB, Canada., Dhalla NS; Institute of Cardiovascular Sciences, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, R3E 0J9 MB, Canada. |
| Abstrakt: |
The activation of the α 1 -adrenoceptor-(α 1 -AR) by norepinephrine results in the G-protein (Gqα) mediated increase in the phosphoinositide-specific phospholipase C (PLC) activity. The byproducts of PLC hydrolytic activity, namely, 1,2-diacylglycerol and inositol-1,4,5-trisphosphate, are important downstream signal transducers for increased protein synthesis in the cardiomyocyte and the subsequent hypertrophic response. In this article, evidence was outlined to demonstrate the role of cardiomyocyte PLC isozymes in the catecholamine-induced increase in protein synthesis by using a blocker of α 1 -AR and an inhibitor of PLC. The discussion was focused on the α 1 -AR-Gqα-PLC-mediated hypertrophic signalling pathway from the viewpoint that it may compliment the other β 1 -AR-G s protein-adenylyl cyclase signal transduction mechanisms in the early stages of cardiac hypertrophy development, but may become more relevant at the late stage of cardiac hypertrophy. From the information provided here, it is suggested that some specific PLC isozymes may potentially serve as important targets for the attenuation of cardiac hypertrophy in the vulnerable patient population at-risk for heart failure. |
