AJP - Renal Physiology, Vol 257, Issue 3 431-F439, Copyright © 1989 by American Physiological Society

ARTICLES

Studies of the mitogenic effect of serotonin in rat renal mesangial cells

N. Takuwa, M. Ganz, Y. Takuwa, R. B. Sterzel and H. Rasmussen
Department of Cell Biology, Yale University School of Medicine, New Haven 06510.

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)

This article has been cited by other articles:

				E. L. Greene, O. Houghton, G. Collinsworth, M. N. Garnovskaya, T. Nagai, T. Sajjad, V. Bheemanathini, J. S. Grewal, R. V. Paul, and J. R. Raymond 5-HT2A receptors stimulate mitogen-activated protein kinase via H2O2 generation in rat renal mesangial cells Am J Physiol Renal Physiol, April 1, 2000; 278(4): F650 - F658. [Abstract] [Full Text] [PDF]

				J. S. Grewal, L. M. Luttrell, and J. R. Raymond G Protein-coupled Receptors Desensitize and Down-regulate Epidermal Growth Factor Receptors in Renal Mesangial Cells J. Biol. Chem., July 13, 2001; 276(29): 27335 - 27344. [Abstract] [Full Text] [PDF]