Quercetin, a phytoestrogen and dietary flavonoid, activates different membrane-bound guanylate cyclase isoforms in LLC-PK1 and PC12 cells.
Resource
J Pharm Pharmacol,55(3),353-358.
Journal
J Pharm Pharmacol
Journal Volume
55
Journal Issue
3
Pages
353-358
Date Issued
2003-03
Date
2003-03
Author(s)
Chen, ZJ
Vetter, M
Chang, GD
Liu, SG
Chang, CH
Abstract
Accumulated evidence suggests that quercetin, a dietary flavonoid, has beneficial effects in protection against cardiovascular diseases and in the inhibition of tumour growth. We have recently shown that antioxidants such as 17β-estradiol, resveratrol, dithiothreitol and vitamin C activate membrane-bound guanylate cyclase GC-A, a receptor for atrial natriuretic factor (ANF). Since quercetin is a phytoestrogen and potent antioxidant, it is possible that it may activate GC-A or other guanylate cyclase isoforms. We examined whether quercetin activates GC-A or GC-B (the receptor for C-type natriuretic peptide, CNP) in PC12 and porcine kidney proximal tubular LLC-PK1 cells. The results showed that quercetin activated a guanylate cyclase isoform in both cell types. Quercetin inhibited CNP-stimulated GC-B activity, but had little effect on ANF-stimulated GC-A activity in PC12 cells, suggesting that quercetin mainly activates GC-B in PC12 cells. In contrast, CNP had no effect on guanylate cyclase activity in LLC-PK1 cells, indicating that GC-B is not expressed in LLC-PK1 cells. Furthermore, quercetin had a small effect on ANF-stimulated GC-A activity and had no effect on soluble guanylate cyclase activity in LLC-PK1 cells, suggesting that quercetin does not activate GC-A, GC-B or soluble guanylate cyclase in LLC-PK1 cells. However, quercetin did stimulate membrane-bound guanylate cyclase activity in LLC-PK1 cell membranes. These results indicate that quercetin activates the GC-B isoform in PC12 cells, but activates an unknown membrane-bound guanylate cyclase isoform in LLC-PK1 cells.
SDGs
Other Subjects
antioxidant; atrial natriuretic factor; flavonoid; guanylate cyclase; isoenzyme; membrane enzyme; natriuretic peptide type C; phytoestrogen; quercetin; animal cell; animal experiment; antioxidant activity; article; cell culture; cell membrane; cell type; controlled study; diet; dose response; drug effect; enzyme activation; enzyme activity; enzyme inhibition; epithelium cell; kidney proximal tubule; kidney tubule cell; membrane binding; nonhuman; pheochromocytoma cell; protein expression; rat; solubility; stimulation; swine; Animals; Atrial Natriuretic Factor; Cyclic GMP; Enzyme Activation; Estrogens, Non-Steroidal; Flavonoids; Guanylate Cyclase; Isoflavones; Isomerism; LLC-PK1 Cells; Membranes; Natriuretic Peptide, C-Type; PC12 Cells; Phytoestrogens; Plant Preparations; Quercetin; Rats; Swine