Evidence that release of adenosine triphosphate from endothelial cells during increased shear stress is vesicular.
In response to increased shear stress, vascular endothelial cells release adenosine triphosphate (ATP) by an unknown mechanism. We have investigated this mechanism using different approaches. First, we discovered that quinacrine, used to locate intracellular stores of ATP bound to peptides, displayed a granular fluorescence, typical of vesicular storage. Second, we found that two inhibitors of vesicular transport (monensin and N-ethylmaleimide) produced a highly significant reduction in the release of ATP from vascular endothelial cells in response to increased shear stress. Preliminary experiments using inhibitors of the cystic fibrosis transmembrane regulator, the sulfonylurea receptor, and the multidrug resistance protein showed no involvement of these ATP-binding cassette transporter proteins (previously characterized in endothelial cells) in the mechanism of release of ATP. We suggest, therefore, that the release of ATP from vascular endothelial cells, like that of nerve cells, is probably by vesicular exocytosis.
Bodin
P
P
Autonomic Neuroscience Institute, Department of Anatomy and Developmental Biology, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, U.K.
Burnstock
G
G
D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors; D000255:Adenosine Triphosphate / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005033:Ethylmaleimide / Q000494:pharmacology; D005089:Exocytosis; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D007700:Kinetics; D008856:Microscopy, Fluorescence; D008985:Monensin / Q000494:pharmacology; D011796:Quinacrine / Q000737:chemistry; D022142:Secretory Vesicles / Q000378:metabolism*; D013314:Stress, Mechanical; D014471:Umbilical Veins / Q000166:cytology; D014700:Verapamil / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate; D008985:Monensin; D014700:Verapamil; D011796:Quinacrine; D005033:Ethylmaleimide; D005905:Glyburide; D002118:Calcium