Studies on ether-phospholipids of vascular smooth muscle cells. Identification of a rapid Ca(2+)-dependent hydrolysis of alkyl-phosphatidylethanolamine promoted by endothelin-l.
We have investigated the metabolism of 1-O-[3H]octadecyl-sn-glycero-3-phosphocholine ([3H]lyso PAF) and [3H] myristic acid in secondary cultures of aortic smooth muscle cells (SMC) to characterize the origin of second messengers generated upon stimulation with endothelin-l (ET-l). When cells were labelled with [3H]lyso PAF, we observed a transfer of the label from phosphatidylcholine (PC) to phosphatidylethanolamine (PE) In contrast, incubation with [3H]lyso PAF labelled mainly alkyl-subclasses while [3H]myristate was associated with diacyl-subclasses. Using these specific labelling procedures, we have shown that ET-l induced a strong hydrolysis of PE. This hydrolysis was specific for alkyl-PE with a maximum after 5 s of stimulation. We have also observed an extracellular Ca(2+)-dependent increase in diglyceride (DG), phosphatidic acid (PA) and mainly triglyceride (TG) concomitant to alkyl-PE hydrolysis. Thus, alkyl-DG generated from alkyl-PE appears to be a major product in ET-l stimulation of SMC. These results suggest a new level of complexity in the signal transduction cascade involving a specificity for phospholipid subclasses.
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Institut National de la Santé et de la Recherche Médicale, Unité 326, Hôpital Purpan, Toulouse, France.
Georgeaud
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Maury
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Cariven
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Prévost
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D000818:Animals; D001013:Aorta, Thoracic; D002118:Calcium / Q000494:pharmacology*; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology*; D006868:Hydrolysis; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000378:metabolism; D015290:Second Messenger Systems; D015398:Signal Transduction; D013552:Swine; D014280:Triglycerides / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D019332:Endothelin-1; D009227:Myristic Acids; C029271:O-deacetyl platelet activating factor; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D010972:Platelet Activating Factor; D014280:Triglycerides; D019814:Myristic Acid; D010738:Type C Phospholipases; D002118:Calcium