Inhibitory Effect of Heparin on Serotonin-induced Hyperplasia and Hypertrophy of Smooth Muscle Cells

Abstract

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.