Document Detail

Quercetin, a phytoestrogen and dietary flavonoid, activates different membrane-bound guanylate cyclase isoforms in LLC-PK1 and PC12 cells.
MedLine Citation:
PMID:  12724041     Owner:  NLM     Status:  MEDLINE    
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 17beta-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.
Zi-Jiang Chen; Michael Vetter; Geen-Dong Chang; Shiguo Liu; Chung-Ho Chang
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of pharmacy and pharmacology     Volume:  55     ISSN:  0022-3573     ISO Abbreviation:  J. Pharm. Pharmacol.     Publication Date:  2003 Mar 
Date Detail:
Created Date:  2003-05-01     Completed Date:  2003-07-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376363     Medline TA:  J Pharm Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  353-8     Citation Subset:  IM    
Department of Medicine, Reproductive Research Center, Shandong Provincial Hospital, Shandong University, Jinan, P. R. China.
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MeSH Terms
Atrial Natriuretic Factor / pharmacology
Cyclic GMP / biosynthesis
Enzyme Activation / drug effects
Estrogens, Non-Steroidal / pharmacology*
Flavonoids / pharmacology*
Guanylate Cyclase / metabolism*
LLC-PK1 Cells
Membranes / drug effects,  enzymology
Natriuretic Peptide, C-Type / pharmacology
PC12 Cells
Plant Preparations
Quercetin / pharmacology*
Grant Support
Reg. No./Substance:
0/Estrogens, Non-Steroidal; 0/Flavonoids; 0/Isoflavones; 0/Phytoestrogens; 0/Plant Preparations; 117-39-5/Quercetin; 127869-51-6/Natriuretic Peptide, C-Type; 7665-99-8/Cyclic GMP; 85637-73-6/Atrial Natriuretic Factor; EC Cyclase

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