Studies of the mitogenic effect of serotonin in rat renal mesangial cells.
A vasoactive inflammatory amine, serotonin, stimulates DNA synthesis in rat glomerular mesangial cells in a dose-dependent manner and acts synergistically with either insulin or epidermal growth factor (EGF). The combined effects of 10(-6) M serotonin and these peptide hormones are nearly equal to those induced by 10% fetal bovine serum. Serotonin stimulates the turnover of polyphosphoinositols resulting in a transient rise in intracellular free Ca2+ concentration, as measured either with the photoprotein aequorin, or with fura-2. This is accompanied by a transient increase in 45Ca2+ efflux from prelabeled cells. Serotonin also induces a prompt and sustained threefold increase in Ca2+ influx rate across the plasma membrane and a rapid and sustained twofold increase in cellular 1,2-diacylglycerol content. In addition, there is an increase in the extent of phosphorylation of an acidic 80-kDa protein, a putative substrate for protein kinase C. Activators of protein kinase C (including phorbol 12-myristate 13-acetate or 1,2-dioctanoylglycerol) mimic the mitogenic effect of serotonin. The effect of serotonin on cell proliferation is partially inhibited in a reversible manner by LiCl. Treatment of mesangial cells with insulin plus EGF for 60 min leads to a small but consistent increase in the content of inositol phosphates and 1,2-diacylglycerol. Their effects are additive to those of serotonin. Moreover, insulin and EGF significantly stimulate the phosphorylation of the 80-kDa protein, and potentiate the serotonin-induced phosphorylation of this protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Takuwa
N
N
Department of Cell Biology, Yale University School of Medicine, New Haven 06510.
Ganz
M
M
Takuwa
Y
Y
Sterzel
R B
RB
Rasmussen
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D003847:Deoxyglucose / Q000096:biosynthesis; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D008934:Mitogens / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism
D007328:Insulin; D008934:Mitogens; D010455:Peptides; D010716:Phosphatidylinositols; D011506:Proteins; D012701:Serotonin; D004815:Epidermal Growth Factor; D004247:DNA; D003847:Deoxyglucose; D011493:Protein Kinase C; D002118:Calcium; D013936:Thymidine