Serotonin produces both hyperplasia and hypertrophy of bovine pulmonary artery smooth muscle cells in culture.
Serotonin [5-hydroxytryptamine (5-HT)] has a dual effect on bovine pulmonary artery smooth muscle cells (SMC) in culture (S.-L. Lee, W. W. Wang, B. J. Moore, and B. L. Fanburg. Circ. Res. 68: 1362-1368, 1991.). Cellular internalization of 5-HT stimulates DNA synthesis and cellular proliferation, whereas the action of 5-HT on a cell surface receptor elevates adenosine 3',5'-cyclic monophosphate and inhibits proliferation. The present study shows that 5-HT causes proliferation of both pulmonary artery and aortic SMC but not of endothelial cells or fibroblasts. Furthermore, c-myc and alpha- and beta-actin gene expressions of pulmonary artery SMC were elevated after 2-h incubation with 5-HT, before stimulation of [3H]thymidine incorporation. Actinomycin D (0.05 micrograms/ml) but not cycloheximide (1 microgram/ml) inhibited the gene expression produced by 5-HT. Growth-arrested SMC progressed from a G0 quiescent state through a normal cell cycle when subjected to 5-HT, 5-HT plus 25 ng/ml insulin-like growth factor, or 5-HT plus 0.5 ng/ml fibroblast growth factor. Cell number increased by 20-40% at 40 h and 50-140% at 7 days. Protein content of cells treated with 5-HT was elevated by 20-40% at 7 days, whereas the rate of protein synthesis, measured by [35S]methionine incorporation, increased by 50-70% at 24 h. In the presence of 1 microM 5-HT, cells enlarged by 70 and 100-200% at 40 h and 7 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Lee
S L
SL
Department of Medicine, New England Medical Center, Boston, Massachusetts 02111.
Wang
W W
WW
Lanzillo
J J
JJ
Fanburg
B L
BL
D000199:Actins / Q000235:genetics; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001483:Base Sequence; D002417:Cattle; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D016259:Genes, myc; D006965:Hyperplasia; D006984:Hypertrophy; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D012701:Serotonin / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D000199:Actins; D015335:Molecular Probes; D012701:Serotonin; D013936:Thymidine