ENDOTHELIN RECEPTORS: EXPRESSION, MODULATION AND ANTAGONISTS: PDF OnlyHamroun Dalil; Mathieu, Marie Noelle; Chevillard, ClaudeJournal of Cardiovascular Pharmacology: 2000 - p S66-S68 Free Abstract Summary: The study reported here characterizes the presence both of endothelin (ET) receptors and of a synthesizing ET apparatus in the human neuroblastoma SK-SY5Y cell line. We demonstrated, using reverse transcriptase polymerase chain reaction (RT-PCR), that these cells bound [125I]ET-1. The potency order of ET analogs to inhibit [125I]ET-1 binding was consistent with the presence of ETA-receptors. [Ca2+]i was increased by both ET-1 and ET-3 (potency order: ET-1 > ET-3. The mRNAs of preproendothelin-1 and of endothelin converting enzyme (ECE) were expressed by cells, as shown by RT-PCR studies. These mRNAs were translated into functional proteins as the cells were able to release mature (1-21) ET-like immunoreactivity into the culture medium. That secretion was time-dependent and was enhanced by treatment of the cells by the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate. These results show that the human SK-SY5Y neuroblastoma cell line produces mature ET which could act as an autocrine/paracrine factor on these cells. Address correspondence and reprint requests to Dr C. Chevillard at INSERM U.469, CCIPE, 141, Rue de la Cardonille, 34094, Montpellier, France. © 2000 Lippincott Williams & Wilkins, Inc.