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Am J Physiol Endocrinol Metab 265: E673-E679, 1993;
0193-1849/93 $5.00
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AJP - Endocrinology and Metabolism, Vol 265, Issue 5 E673-E679, Copyright © 1993 by American Physiological Society

ARTICLES

Interaction of PDGF and natriuretic peptides on mesangial cell proliferation and endothelin secretion

M. Kohno, M. Ikeda, M. Johchi, T. Horio, K. Yasunari, N. Kurihara and T. Takeda
First Department of Internal Medicine, Osaka City University Medical School, Japan.

The present study examined the possible interaction of platelet-derived growth factor (PDGF) and atrial or brain natriuretic peptides (ANP and BNP, respectively) on cellular proliferation and secretion of endothelin-1 in cultured rat mesangial cells. PDGF increased cellular proliferation and endothelin-1 secretion. The protein kinase C (PKC) inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, staurosporine, and PKC inhibitor peptide, inhibited such stimulation. Rat ANP-(1-28) and rat BNP-45 exhibited clearly dose-related inhibition of PDGF-stimulated cellular proliferation and endothelin-1 secretion. This inhibition by ANP and BNP was paralleled by an increase in the cellular level of guanosine 3',5'-cyclic monophosphate (cGMP). Results indicate that PDGF stimulates cellular proliferation and endothelin-1 secretion in cultured rat mesangial cells by a mechanism probably involving activation of PKC and that ANP and BNP inhibit such stimulation through a cGMP-dependent process.


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