Serotonin-induced deoxyribonucleic acid synthesis in vascular smooth muscle cells involves a novel, pertussis toxin-sensitive pathway.
Serotonin-induced DNA synthesis in bovine aortic smooth muscle cells was totally abolished by pretreatment of cultures with 5 ng/ml pertussis toxin. The half maximally effective concentration of toxin was approximately 10 pg/ml. Pertussis toxin did not affect platelet-derived growth factor (PDGF)-stimulated DNA synthesis and actually enhanced the mitogenic effect of the phorbol ester, phorbol 12-myristate 13-acetate. Pertussis toxin did not inhibit serotonin-stimulated inositol phosphate accumulation or increases in intracellular calcium or cAMP concentrations under conditions sufficient to completely inhibit serotonin-induced (3H)thymidine incorporation. These results demonstrate that a novel, pertussis-sensitive pathway is required for serotonin-, but not platelet-derived growth factor-induced DNA synthesis in vascular smooth muscle cells. The pertussis-sensitive step does not involve cAMP, phosphoinositide hydrolysis, mobilization of intracellular calcium, or phorbol ester-sensitive protein kinase C activity.
Kavanaugh
W M
WM
Howard Hughes Medical Institute, University of California, San Francisco 94143.
Williams
L T
LT
Ives
H E
HE
Coughlin
S R
SR
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured / Q000187:drug effects; D000242:Cyclic AMP / Q000096:biosynthesis / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis* / Q000187:drug effects; D006868:Hydrolysis; D008938:Mitosis / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D001095:Arachidonic Acids; D010716:Phosphatidylinositols; D010566:Virulence Factors, Bordetella; D012701:Serotonin; D004247:DNA; D000242:Cyclic AMP; D037342:Pertussis Toxin; D002118:Calcium