Effects of endothelins on the human megakaryoblastic cell line MEG-01.
Some effects of endothelin-1 (ET-1) were studied on the megakaryoblastic cell line MEG-01. ET-1 induced an elevation of the intracellular levels of Ca2+([Ca2+]i) as measured with the fluorescent indicator indo-1, which consists of an initial transient increase and an ensuing sustained plateau. The plateau phase was abolished by removal of extracellular Ca2+. In addition, ET-1 induced a rapid (within 5 s) increase in the accumulation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and more delayed increases in Ins(1,3,4)P3 and Ins(1,3,4,5)P4, but did not modify cAMP levels. ET-1 homologues (ET-2, ET-3, sarafotoxin 6b and vasointestinal constrictor) also induced biphasic effects on [Ca2+]i. The Ca2+ elevation was concentration dependent, the order of potency being sarafotoxin 6b > ET-1 > ET-2 = vasointestinal constrictor > ET-3. The actions of ET analogs in raising [Ca2+]i were mutually exclusive, suggesting that they act through the same mechanism. These results suggest that cells of the megakaryoblast/megakaryocyte lineage are targets for endothelins.
Diochot
S
S
INSERM U. 300, Faculté de Pharmacie, Montpellier, France.
Vittet
D
D
Mathieu
M N
MN
Launay
J M
JM
Chevillard
C
C
D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology*; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D007947:Leukemia, Megakaryoblastic, Acute / Q000378:metabolism*; D008533:Megakaryocytes / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014757:Viper Venoms / Q000378:metabolism*
D016232:Endothelins; D007295:Inositol Phosphates; D014757:Viper Venoms; C057354:sarafotoxins s6; D000242:Cyclic AMP; D002118:Calcium