Glycolytic activity and enhancement of serotonin uptake by endothelial cells exposed to hypoxia/anoxia.
Serotonin (5-HT) uptake by bovine pulmonary artery endothelial cells in culture was stimulated several fold by exposure of cells for 24 hours to 0-3% O2. The cells appeared normal morphologically, excluded trypan blue dye, showed normal levels of release of lactate dehydrogenase, and contained normal amounts of adenosine triphosphate (ATP). Incubation of cells with iodoacetate (3-5 microM), an inhibitor of glycolytic metabolism, prevented the stimulation of 5-HT uptake but did not impair cellular proliferation. A similar, but less pronounced, effect was produced by 1 mM deoxyglucose. On the other hand, the mitochondrial inhibitors antimycin A, sodium azide, potassium cyanide, and 2,4-dinitrophenol inhibited cellular replication similar to the effect of anoxia but did not alter the stimulation of 5-HT uptake. 5-HT uptake correlated strongly with lactate production by the cells exposed to anoxia (r = 0.98). We conclude that stimulation of 5-HT uptake by prolonged exposure of the endothelial cell to hypoxia/anoxia causes alteration of a membrane function (serotonin transport) of the endothelial cell. This alteration is associated with enhanced glycolytic activity of the cell during exposure to hypoxia. The mechanism for translation of enhanced glycolysis to later stimulation of 5-HT uptake remains to be determined. Endothelial cellular replication is dependent on aerobic metabolism.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D000860:Hypoxia / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008660:Metabolism / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*
D007773:Lactates; D012701:Serotonin; D019344:Lactic Acid; D000255:Adenosine Triphosphate