PDGF activates K-Cl cotransport through phosphoinositide 3-kinase and protein phosphatase-1 in primary cultures of vascular smooth muscle cells.
K-Cl cotransport (K-Cl COT, KCC) is an electroneutrally coupled movement of K and Cl present in most cells. In this work, we studied the pathways of regulation of K-Cl COT by platelet-derived growth factor (PDGF) in primary cultures of vascular smooth muscle cells (VSMCs). Wortmannin and LY 294002 blocked the PDGF-induced K-Cl COT activation, indicating that the phosphoinositide 3-kinase (PI 3-K) pathway is involved. However, PD 98059 had no effect on K-Cl COT activation by PDGF, suggesting that the mitogen-activated protein kinase pathway is not involved under the experimental conditions tested. Involvement of phosphatases was also examined. Sodium orthovanadate, cyclosporin A and okadaic acid had no effect on PDGF-stimulated K-Cl COT. Calyculin A blocked the PDGF-stimulated K-Cl COT by 60%, suggesting that protein phosphatase-1 (PP-1) is a mediator in the PDGF signaling pathway/s. In conclusion, our results indicate that the PDGF-mediated pathways of K-Cl COT regulation involve the signaling molecules PI 3-K and PP-1.
Zhang
Jing
J
Department of Pharmacology & Toxicology, Wright State University, School of Medicine, Dayton, OH 45435, USA.
Lauf
Peter K
PK
Adragna
Norma C
NC
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000077214:Becaplermin; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D008387:Marine Toxins; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D009025:Morpholines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D019319:Okadaic Acid / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology / Q000502:physiology*; D011188:Potassium / Q000378:metabolism*; D054645:Protein Phosphatase 1; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology; D000077191:Wortmannin; D000096922:K Cl- Cotransporters
D000730:Androstadienes; D000077214:Becaplermin; D002712:Chlorides; D002867:Chromones; D016572:Cyclosporine; D005419:Flavonoids; D008387:Marine Toxins; D020929:Mitogen-Activated Protein Kinase Kinases; D009025:Morpholines; D019319:Okadaic Acid; D010080:Oxazoles; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010749:Phosphoprotein Phosphatases; D010982:Platelet-Derived Growth Factor; D011188:Potassium; D054645:Protein Phosphatase 1; D020574:Proto-Oncogene Proteins c-sis; D027981:Symporters; D014638:Vanadates; D000077191:Wortmannin; D000096922:K Cl- Cotransporters; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C059041:calyculin A; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one