Synergistic Stimulation of Aldosterone Production in Human Adrenocortical Carcinoma NCI-H295R Cells by Endothelin-1 and Angiotensin II
| Autor: | Chii-Whei Hu, Randy Lee Webb, Arco Y. Jeng |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Serum
medicine.medical_specialty Endothelin A Receptor Antagonists medicine.drug_class Stimulation Peptides Cyclic chemistry.chemical_compound Cell Line Tumor Internal medicine Adrenocortical Carcinoma medicine Humans Adrenocortical carcinoma Aldosterone Endothelin-2 Pharmacology Endothelin-3 Angiotensin II receptor type 1 Dose-Response Relationship Drug Endothelin-1 Chemistry Angiotensin II Receptor Endothelin A medicine.disease Receptor antagonist Receptor Endothelin B Endothelin 1 Adrenal Cortex Neoplasms Endothelin B Receptor Antagonists Up-Regulation Endocrinology Secretagogue Cardiology and Cardiovascular Medicine |
| Zdroj: | Journal of Cardiovascular Pharmacology. 44:S289-S292 |
| ISSN: | 0160-2446 |
| DOI: | 10.1097/01.fjc.0000166276.32421.1d |
| Popis: | Aldosterone has recently been implicated in the pathogenesis of heart failure. The purpose of the present study was to determine the effect of endothelin-1 (ET-1) and angiotensin II (Ang II), two potent vasoconstrictors that are also involved in heart failure, on aldosterone secretion by human adrenocortical carcinoma NCI-H295R cells grown in 96-well plates. Ang II stimulated the production of aldosterone dose-dependently in serum-free medium, and the presence of serum drastically decreased aldosterone secretion. In contrast, ET-1-stimulated aldosterone production absolutely required serum. Under optimal conditions, ET-1 was more effective than Ang II as an aldosterone secretagogue. In a suboptimal condition of 2.5% serum, ET-1 and Ang II at 1 μM produced 63 and 76 pmol aldosterone/mg protein, respectively, while 230 pmol aldosterone/mg protein was generated upon co-incubation with ET-1 and Ang II. The effect of ET-1 was inhibited dose-dependently by the selective ET A receptor antagonist BQ-123 with an IC 5 0 of 23 nM, but the selective ET B receptor antagonist RES-701 had no effect up to 10 μM. These results suggest that ET-1 and Ang II stimulated aldosterone secretion synergistically in NCI-H295R cells and that the effect of ET-1 was mediated via the ET A receptor subtype. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|