Dual effect of serotonin on growth of bovine pulmonary artery smooth muscle cells in culture. Circ. Res

We have previously reported that serotonin (5-hydroxytryptamine [SHT]) alters cultured bovine pulmonary artery smooth muscle cell (SMC) configuration through two different regulatory mechanisms. We now report that 5HT also regulates SMC growth through these same two mechanisms-a stimulatory event initiated intracellularly and inhibition of growth resulting from a cell surface action. 5HT (1,M) plus 0.1 mM iproniazid (a 5HT metabolic inhibitor) produced a severalfold stimulation of DNA synthesis (as measured by ['H]thymidine incorpo-ration) of SMCs after a 17-24-hour incubation with only a slight elevation of cellular cAMP. This stimulatory effect responded synergistically with other growth factors including platelet-derived growth factor, fibroblast growth factor, and epidermal growth factor and was effectively reversed by 5HT uptake inhibition. It was not produced by 5-hydroxyindoleacetic acid, a metabolite of 5HT. In the presence of 1 pM 5HT plus 0.1 mM isobutylmethylxanthine (IBMX), cAMP was elevated eightfold, dendritic formation occurred, and ['H]thymidine labeling of SMCs was inhibited. Inhibition of labeling by ['H]thymidine was mimicked by other agents that elevated cellular cAMP (10,uM histamine, 1,M isoproterenol plus 0.1 mM IBMX, and 10,uM forskolin) and by 1 mM dibutyryl cAMP. This inhibitory effect was not blocked by eithe