Autocrine-paracrine role of endothelin-1 in the regulation of aldosterone synthase expression and intracellular Ca2+ in human adrenocortical carcinoma NCI-H295 cells. 1997

G P Rossi, and G Albertin, and S Bova, and A S Belloni, and F Fallo, and U Pagotto, and L Trevisi, and G Palù, and A C Pessina, and G G Nussdorfer
Department of Clinical and Experimental Medicine, University of Padua Medical School, Padova, Italy. gprossi@ipdunidx.unipd.it

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.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008666 Metalloendopeptidases ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism. Metallo-Endoproteinases,Metalloendopeptidase
D009842 Oligopeptides Peptides composed of between two and twelve amino acids. Oligopeptide
D010880 Piperidines A family of hexahydropyridines.
D011498 Protein Precursors Precursors, Protein
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072396 Endothelin-Converting Enzymes Metalloendopeptidases which convert BIG ENDOTHELIN to ENDOTHELIN-1. ECE-1beta,Endothelin Converting Enzyme,Endothelin Converting Enzyme-1a,Endothelin-Converting Enzyme,Endothelin-Converting Enzyme 1,Endothelin-Converting Enzyme 2,Endothelin-Converting Enzyme II,Endothelin-Converting Enzyme-1b,Endothelin-Converting Metalloprotease 2,Metalloprotease ECE-2,ECE-2, Metalloprotease,Endothelin Converting Enzyme 1,Endothelin Converting Enzyme 1a,Endothelin Converting Enzyme 1b,Endothelin Converting Enzyme 2,Endothelin Converting Enzyme II,Endothelin Converting Enzymes,Endothelin Converting Metalloprotease 2,Metalloprotease ECE 2
D000306 Adrenal Cortex Neoplasms Tumors or cancers of the ADRENAL CORTEX. Adrenocortical Cancer,Cancer of Adrenal Cortex,Adrenal Cortex Cancer,Cancer of the Adrenal Cortex,Neoplasms, Adrenal Cortex,Adrenal Cortex Cancers,Adrenal Cortex Neoplasm,Adrenocortical Cancers,Cancer, Adrenal Cortex,Cancer, Adrenocortical,Cancers, Adrenal Cortex,Cancers, Adrenocortical,Neoplasm, Adrenal Cortex
D001345 Autoradiography The making of a radiograph of an object or tissue by recording on a photographic plate the radiation emitted by radioactive material within the object. (Dorland, 27th ed) Radioautography

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