Effects of endothelins on the human megakaryoblastic cell line MEG-01

• Published in: European journal of pharmacology Vol. 227; no. 4; p. 427
• Main Authors: Diochot, S, Vittet, D, Mathieu, M N, Launay, J M, Chevillard, C
• Format: Journal Article
• Language: English
• Published: Netherlands 01.12.1992
• Subjects: Calcium - metabolism; Cell Line; Cyclic AMP - metabolism; Endothelins - pharmacology; Humans; Inositol Phosphates - metabolism; Leukemia, Megakaryoblastic, Acute - metabolism; Megakaryocytes - drug effects; Megakaryocytes - metabolism; Tumor Cells, Cultured; Viper Venoms - metabolism
• DOI: 10.1016/0922-4106(92)90161-N
• ISSN: 0014-2999

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.