Superoxide as an intermediate signal for serotonin-induced mitogenesis.
Serotonin (5-HT) stimulates tyrosine phosphorylation and proliferation of bovine pulmonary artery smooth muscle cells (SMC) through its active transport (Lee et al, 1991). The present studies show that 5-HT also rapidly elevates O2.- formation by these cells within 10 minutes as measured by a lucigenin-enhanced chemiluminescence assay. The O2.- free radical quencher, Tiron, and N-acetyl-cysteine, a substrate for glutathione, block both the 5-HT-induced formation of O2.- and cellular proliferation. Similarly, inhibition of 5-HT transport with imipramine or treatment of cells with diphenyliodonium, a NAD(P)H oxidase inhibitor, block both 5-HT-induced elevation of O2.- and cellular proliferation. Alpha-hydroxyfarnesylphosphonic acid, an inhibitor of p21ras, also blocks 5-HT-induced proliferation. Endothelial cells from the same vessel show neither 5-HT-induced proliferation nor stimulation of O2.- formation. We conclude that 5-HT induced cellular proliferation of SMC through signaling pathways that utilize its transport system and O2.- formation.
Lee
S L
SL
Pulmonary and Critical Care Division/Department of Medicine/Tupper Research Institute/New England Medical Center/Tufts University School of Medicine, Boston, MA 02111, USA.
Wang
W W
WW
Fanburg
B L
BL
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D008163:Luminescent Measurements; D008938:Mitosis / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D012701:Serotonin / Q000494:pharmacology*; D015398:Signal Transduction / Q000502:physiology*; D013268:Stimulation, Chemical; D013481:Superoxides / Q000378:metabolism*
D013481:Superoxides; D012701:Serotonin