Inhibitory effect of heparin on serotonin-induced hyperplasia and hypertrophy of smooth muscle cells.
Serotonin (5-HT) produces both hyperplastic and hypertrophic effects on smooth muscle cell (SMC) in culture. Heparin is known to inhibit serum-induced hyperplasia of SMC but has not been previously tested on the stimulatory effect of 5-HT on SMC. Our present data show that at 24 h heparin inhibited by 50% the stimulation of 3H-thymidine incorporation into bovine pulmonary artery SMC and at 7 days totally reversed both cellular proliferation and enlargement of SMC produced by 1 microM 5-HT. Heparin failed to alter 5-HT uptake by SMC, but inhibited the stimulation of tyrosine phosphorylation of GTPase-activating protein, a proposed intermediate in the 5-HT stimulatory process. Thus heparin inhibits both hyperplastic and hypertrophic effects of 5-HT on SMC, perhaps through the inhibition of a phosphorylated intermediate protein.
Lee
S L
SL
Department of Medicine, New England Medical Center/Tufts University School of Medicine, Boston, MA 02111, USA.
Wang
W W
WW
Joseph
P M
PM
Hales
C A
CA
Fanburg
B L
BL
D000818:Animals; D001692:Biological Transport; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D006493:Heparin / Q000494:pharmacology*; D006965:Hyperplasia; D006984:Hypertrophy; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012701:Serotonin / Q000378:metabolism / Q000633:toxicity*; D012702:Serotonin Antagonists; D013936:Thymidine / Q000378:metabolism
D012702:Serotonin Antagonists; D012701:Serotonin; D006493:Heparin; D004247:DNA; D013936:Thymidine