Enhancement of the endothelial production of prostacyclin by substituted derivatives of BAPTA-AM
European Journal of Pharmacology, ISSN: 0014-2999, Vol: 233, Issue: 1, Page: 13-20
1993
- 15Citations
- 5Captures
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Metrics Details
- Citations15
- Citation Indexes15
- 15
- CrossRef12
- Captures5
- Readers5
Article Description
Our observation that loading of bovine endothelial cells quin 2 or 1,2-bis(O-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA) enhances their release of prostacyclin (PGI 2 ) has been studied in detail. The action of the acetoxymethyl ester (AM) of BAPTA (BAPTA-AM) was biphasic: at high concentrations (50 μM) and after prolonged exposure (60 min or more), it behaved as an inhibitor instead of an amplifier. Since inhibiton could be related to calcium chelation, we tested 5,5′-difluoro-BAPTA-AM (5FBAPTA-AM), 4,4′-difluoro-BAPTA-AM (4FBAPTA-AM) and 5,5′-dibromo-BAPTA-AM (5BBAPTA-AM), whose corresponding free acids have a reduced affinity for Ca 2+ : these compounds were much more active in enhancing PGI 2 production than BAPTA-AM itself. The effect of 5BBAPTA-AM was detectable at 0.5 μM and almost maximal at 5 μM (5-fold increase). 5BBAPTA-AM increased the release of free arachidonate induced by ATP but had no effect on the generation of inositol phosphates, the release of choline metabolites, and the accumulation of cAMP. 5BBAPTA-AM had a cytotoxic effect on the endothelial cells only after prolonged exposure to a high (50 μM) concentration. 5BBAPTA-AM inhibited the platelet production of thromboxane stimulated by a high (0.5 U/ml) concentration of thrombin and slightly potentiated the effect of a low (0.005 U/ml) concentration. In conclusion, the effect of 5BBAPTA-AM on the production of PGI 2 seems to be rather specific to arachidonate metabolism in endothelial cells.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/001429999390343G; http://dx.doi.org/10.1016/0014-2999(93)90343-g; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0027467035&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/8386085; http://linkinghub.elsevier.com/retrieve/pii/001429999390343G; http://api.elsevier.com/content/article/PII:001429999390343G?httpAccept=text/xml; http://api.elsevier.com/content/article/PII:001429999390343G?httpAccept=text/plain; https://linkinghub.elsevier.com/retrieve/pii/001429999390343G; http://dx.doi.org/10.1016/0014-2999%2893%2990343-g; https://dx.doi.org/10.1016/0014-2999%2893%2990343-g
Elsevier BV
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