Endothelial cell inhibition of hypoxia-induced stimulation of serotonin uptake by vascular smooth muscle cells.
Exposure of bovine pulmonary artery smooth muscle cells (SMC) to anoxia for 24 h resulted in an approximate twofold stimulation of serotonin (5-HT) uptake compared with SMC exposed to 20% O2. The stimulation of 5-HT uptake by exposure to anoxia was eliminated when bovine pulmonary artery endothelial cells (EC) were cocultured with SMC. Incubation with EC-conditioned medium produced similar inhibitory effects on 5-HT uptake of SMC exposed to anoxia, a result not seen with SMC-conditioned medium. The inhibitory effect of EC-conditioned medium on the anoxia-stimulated 5-HT uptake was concentration dependent and absent at a dilution of 1:16. The production of the inhibitor was time-dependent. The EC-derived inhibitory factor was heat-stable at 100 degrees C for as long as 10 min and was stable in a pH range from 5.0 to 10.0. Significant losses of inhibitory activity of EC-conditioned medium were observed after treatment with trypsin, pronase E, and proteinase K. The molecular weight on the inhibitory factor from EC-conditioned medium was estimated to be approximately 66,000 by size-exclusion chromatography. The data show that stimulated uptake of 5-HT by SMC under anoxic conditions is under regulation by a protein (or polypeptide) produced by EC.
Yu
F S
FS
Department of Medicine, New England Medical Center Hospital, Boston, Massachusetts.
Lee
S L
SL
Lanzillo
J J
JJ
Fanburg
B L
BL
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002845:Chromatography; D003470:Culture Media; D004730:Endothelium, Vascular / Q000032:analysis / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D008970:Molecular Weight; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010101:Oxygen Consumption; D011506:Proteins / Q000032:analysis; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000032:analysis
D003470:Culture Media; D011506:Proteins; D012702:Serotonin Antagonists; D012701:Serotonin