Enhanced release of prostacyclin from quin 2-loaded endothelial cells.
The acetoxymethyl ester (AM) of quin-2 (quin-2/AM) enhanced the release of prostacyclin (PGI2) from bovine aortic endothelial cells stimulated by ATP, bradykinin or ionophore A23187. It also increased the mobilization of free arachidonic acid in response to ATP. Ca2+-clamping with a combination of EGTA and quin-2/AM abolished the response to ATP. The effect of quin-2/AM was mimicked by a structural analog, the acetoxymethyl ester of 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA/AM), but not by the heavy metal chelator, tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) and only slightly by fura-2/AM. The mechanism of this pharmacological action of quin-2/AM and its potential for the design of PGI2-stimulating drugs remain to be explored.
Raspe
E
E
Institute of Interdisciplinary Research, School of Medicine, Free University of Brussels, Belgium.
Ramboer
I
I
Galand
N
N
Boeynaems
J M
JM
D000227:Adenine Nucleotides / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D015232:Dinoprostone / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D013997:Time Factors
D000227:Adenine Nucleotides; D000634:Aminoquinolines; D001095:Arachidonic Acids; D016718:Arachidonic Acid; C035738:Quin2-acetoxymethyl ester; D015232:Dinoprostone; D001920:Bradykinin; D002118:Calcium