Interaction of PDGF and natriuretic peptides on mesangial cell proliferation and endothelin secretion.
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.
Kohno
M
M
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Ikeda
M
M
Johchi
M
M
Horio
T
T
Yasunari
K
K
Kurihara
N
N
Takeda
T
T
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000096:biosynthesis* / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D019311:Staurosporine; D013936:Thymidine / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D000470:Alkaloids; D016232:Endothelins; D007546:Isoquinolines; D009419:Nerve Tissue Proteins; D010879:Piperazines; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D020097:Natriuretic Peptide, Brain; D009599:Nitroprusside; D015124:8-Bromo Cyclic Adenosine Monophosphate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D009320:Atrial Natriuretic Factor; D004247:DNA; D011493:Protein Kinase C; D019311:Staurosporine; D013936:Thymidine