Potential role for triglycerides in signal transduction

We previously reported that endothelin-1 or platelet-derived growth factor promoted in aortic smooth muscle cells a rapid hydrolysis of 1-O-alkyl-2-ac yl-sn-glycero-3-phosphoethanolamine (alkyl-PE) which was immediately conver ted into 1-O-alkyl-2,3-diacyl-sn-glycerol (alkyl-TG) within 5 s or 60 s res pectively [C. Comminges et al, (1996) Biochem, Biophys. Res. Commun. 220, 1 008-1013 and C, Comminges et al, (1997) Biochim, Biophys. Acta 1355, 69-80] , Tn this study, we show that this alkyl-PE hydrolysis is triggered by a tr ansient activation of a specific phospholipase C (PLC) regulated by pertuss is toxin-sensitive heterotrimeric G-proteins, Moreover, this PLC can be tri ggered through a Ca2+ influx depending on L-ty pe Ca2+ channel activation, as suggested by the use of a specific 'activator' S(-)-BayK 8644 and of sel ective inhibitors such as nimodipine, Interestingly, low concentrations (10 (-8)-10(-7) M) of alkyl-TG block the opening of L-type Ca2+ channels, where as identical concentrations of DG do not alter L-type Ca2+ channels. This s tudy thus unravels a hitherto unrecognized signaling pathway generating alk yl-TG as a novel lipid second messenger, potentially acting as a negative f eedback regulator of L-type Ca2+ channels. (C) 2000 Federation of European Biochemical Societies.