Open AccessAutocrine-Paracrine Role of Endothelin-1 in the Regulation of Aldosterone Synthase Expression and Intracellular Ca2+in Human Adrenocortical Carcinoma NCI-H295 Cells1
Author(s) -
Gian Paolo Rossi,
Giovanna Albertin,
Sergio Bova,
Anna S. Belloni,
Francesco Fallo,
Uberto Pagotto,
Lucia Trevisi,
Giorgio Palú,
Achille C. Pessina,
Gastone G. Nussdorfer
Publication year - 1997
Publication title -
endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.674
H-Index - 257
eISSN - 1945-7170
pISSN - 0013-7227
DOI - 10.1210/endo.138.10.5267
Subject(s) - autocrine signalling , paracrine signalling , endocrinology , medicine , adrenocortical carcinoma , biology , aldosterone , receptor , endothelin 1 , aldosterone synthase , microbiology and biotechnology , renin–angiotensin system , blood pressure
The role played by endothelin (ET-1) and its receptor subtypes A and B (ET(A) and ET(B)) in the functional regulation of human NCI-H295 adrenocortical carcinoma cells has been investigated. Reverse transcription-PCR with primers specific for prepro-ET-1, human ET-1 converting enzyme-1, ET(A), and ET(B) complementary DNAs consistently demonstrated the expression of all genes in NCI-H295 cells. The presence of mature ET-1 and both its receptor subtypes was confirmed by immunocytochemistry and autoradiography, respectively. Aldosterone synthase (AS) messenger RNA was also detected in NCI-H295 cells, and AS gene expression was enhanced by both ET-1 and the specific ET(B) agonist IRL-1620; this effect was not inhibited by either the ET(A) antagonist BQ-123 or the ET(B) antagonist BQ-788. A clear-cut increase in the intracellular Ca2+ concentration in NCI-H295 cells in response to ET(B), but not ET(A), activation was observed. In light of these findings, the following conclusions can be drawn: 1) NCI-H295 cells possess an active ET-1 biosynthetic pathway and are provided with ET(A) and ET(B) receptors; 2) ET-1 regulates in an autocrine/paracrine fashion the secretion of aldosterone by NCI-H295 cells by enhancing both AS transcription and raising the intracellular Ca2+ concentration; and 3) the former effect of ET-1 probably involves the activation of both receptor subtypes, whereas calcium response is exclusively mediated by the ET(B) receptor.