Stimulation of aortic smooth muscle cell mitogenesis by serotonin.
Bovine aortic smooth muscle cells in vitro responded to 1 nM to 10 microM serotonin with increased incorporation of [3H]thymidine into DNA. The mitogenic effect of serotonin was half-maximal at 80 nM and maximal above 1 microM. At a concentration of 1 microM, serotonin stimulated smooth muscle cell mitogenesis to the same extent as human platelet-derived growth factor (PDGF) at 12 ng/ml. Tryptamine was approximately 1/10th as potent as serotonin as a mitogen for smooth muscle cells. Other indoles that are structurally related to serotonin (D- and L-tryptophan, 5-hydroxy-L-tryptophan, N-acetyl-5-hydroxytryptamine, melatonin, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophol) and quipazine were inactive. The stimulatory effect of serotonin on smooth muscle cell DNA synthesis required prolonged (20-24 hr) exposure to the agonist and was attenuated in the presence of serotonin D receptor antagonists. When smooth muscle cells were incubated with submaximal concentrations of serotonin and PDGF, synergistic rather than additive mitogenic responses were observed. These data indicate that serotonin has a significant mitogenic effect on smooth muscle cells in vitro, which appears to be mediated by specific plasma membrane receptors.
Nemecek
G M
GM
Coughlin
S R
SR
Handley
D A
DA
Moskowitz
M A
MA
D000818:Animals; D001011:Aorta / Q000502:physiology; D002417:Cattle; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D008934:Mitogens; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D004247:DNA; D013936:Thymidine