Document Detail


Inhibition of type 4 phosphodiesterase by rolipram and Ginkgo biloba extract (EGb 761) decreases agonist-induced rises in internal calcium in human endothelial cells.
MedLine Citation:
PMID:  10978267     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effects of Gingko biloba extract EGb 761 on 5 isolated, vascular, cyclic nucleotide phosphodiesterase (PDE) isoforms were evaluated. EGb 761 preferentially inhibited PDE4 (IC(50)=25.1 mg/L), the isoform that is mainly present in endothelial cells, in a competitive manner (K:(i)=12.5 mg/L). Because changes in cyclic nucleotide levels may affect intracellular calcium ([Ca(2+)](i)) levels in endothelial cells, we examined the effects of EGb 761 on both resting [Ca(2+)](i) levels and agonist-induced rises in [Ca(2+)](i) in single human umbilical vein endothelial cells (HUVECs) in culture. The effects of EGb 761 were compared with those of rolipram, a selective PDE4 inhibitor that increases cellular cAMP levels, and the cAMP analogue dibutyryl cAMP (db-cAMP). EGb 761 (20 and 100 mg/L), rolipram (50 micromol/L), and db-cAMP (100 micromol/L) significantly inhibited histamine-, ATP-, and thrombin-induced [Ca(2+)](i) increases in HUVECs without modifying resting [Ca(2+)](i) levels. Similar results were obtained by using a Ca(2+)-free bath solution. EGb 761 (100 mg/L), but not rolipram (50 micromol/L) or db-cAMP (100 micromol/L), also inhibited Ca(2+) influx into cells having thapsigargin-depleted internal Ca(2+) stores and bathed in a Ca(2+)-free external solution. Our results are consistent with an inhibition of PDE activity that causes a reduction of agonist-induced increases in [Ca(2+)](i) in HUVECs, mainly by inhibition of Ca(2+) mobilization from internal stores. It thus may be that the cardiovascular effects of EGb 761 involve inhibition of PDE4 activity and subsequent modification of Ca(2+) signaling in endothelial cells.
Authors:
M Campos-Toimil; C Lugnier; M T Droy-Lefaix; K Takeda
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  20     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2000 Sep 
Date Detail:
Created Date:  2000-10-12     Completed Date:  2000-10-12     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  E34-40     Citation Subset:  IM    
Affiliation:
Pharmacologie et Physico-chimie des Interactions Cellulaires et Moléculaires, UMR CNRS 7034, Faculté de Pharmacie, Université Louis Pasteur de Strasbourg, Illkirch, France.
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MeSH Terms
Descriptor/Qualifier:
3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
Antioxidants / pharmacology
Biological Transport / drug effects
Bucladesine / pharmacology
Calcium / metabolism*
Cells, Cultured
Cyclic Nucleotide Phosphodiesterases, Type 4
Endothelium, Vascular / drug effects*,  enzymology,  metabolism
Flavonoids / pharmacology*
Ginkgo biloba
Humans
Phosphodiesterase Inhibitors / pharmacology*
Plant Extracts*
Rolipram / pharmacology*
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Flavonoids; 0/Ginkgo biloba extract 761; 0/Phosphodiesterase Inhibitors; 0/Plant Extracts; 362-74-3/Bucladesine; 61413-54-5/Rolipram; 7440-70-2/Calcium; EC 3.1.4.17/3',5'-Cyclic-AMP Phosphodiesterases; EC 3.1.4.17/Cyclic Nucleotide Phosphodiesterases, Type 4

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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