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Am J Physiol Lung Cell Mol Physiol 266: L46-L52, 1994;
1040-0605/94 $5.00
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AJP - Lung Cellular and Molecular Physiology, Vol 266, Issue 1 46-L52, Copyright © 1994 by American Physiological Society


ARTICLES

Serotonin produces both hyperplasia and hypertrophy of bovine pulmonary artery smooth muscle cells in culture

S. L. Lee, W. W. Wang, J. J. Lanzillo and B. L. Fanburg
Department of Medicine, New England Medical Center, Boston, Massachusetts 02111.

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)


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