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Regulation of natriuretic peptide (urodilatin) release in a human kidney cell line.
- Source :
-
Kidney international [Kidney Int] 1999 Jan; Vol. 55 (1), pp. 91-9. - Publication Year :
- 1999
-
Abstract
- Background: To identify the molecular mechanisms underlying the release of a renal natriuretic peptide (NP) we selected a human kidney cell line (HEK 293) that displays several characteristics of distal tubular cells.<br />Methods: Cells were exposed to different extracellular and intracellular stimuli, and the effect on NP release was measured with a specific urodilatin radioimmunoassay, as well as with an atrial NP (ANP) radioimmunoassay.<br />Results: In the absence of stimuli, HEK 293 cells showed a basal release of urodilatin immunoreactivity and ANP immunoreactivity. Raising the osmolality of the secretion medium with sodium chloride and various other osmolytes rapidly increased cellular NP secretion. Elevation of intracellular cAMP levels by forskolin plus 3-isobutyl-1-methylxanthine and administration of phorbol-12-myristate-13-acetate together with the calcium-ionophore A23187 also resulted in respective increases in the amount of secreted peptide. HEK 293 cells exhibit the endogenous expression of both particulate and soluble guanylyl cyclases. In the presence of 8-Br-cGMP, cell cultures showed the enhanced secretion of an ANP immunoreactive peptide only, indicating that guanylyl cyclase activation provoked the secretion of ANP immunoreactivity but not of urodilatin immunoreactivity.<br />Conclusions: The human embryonic kidney cell line HEK 293 represents a renal cellular model system in which we have identified a rapid and regulated release of NPs in response to the osmotic effect of increased extracellular sodium chloride and various intracellular stimuli.
- Subjects :
- 1-Methyl-3-isobutylxanthine pharmacology
Calcimycin pharmacology
Cell Line
Colforsin pharmacology
Culture Media
Cyclic AMP metabolism
Cyclic GMP analogs & derivatives
Cyclic GMP biosynthesis
Cyclic GMP pharmacology
Guanylate Cyclase metabolism
Humans
Intracellular Fluid drug effects
Intracellular Fluid metabolism
Kidney drug effects
Osmolar Concentration
Radioimmunoassay
Tetradecanoylphorbol Acetate pharmacology
Atrial Natriuretic Factor metabolism
Kidney metabolism
Peptide Fragments metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0085-2538
- Volume :
- 55
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Kidney international
- Publication Type :
- Academic Journal
- Accession number :
- 9893117
- Full Text :
- https://doi.org/10.1046/j.1523-1755.1999.00242.x