Different effects of platelet-derived growth factor isoforms on rat vascular smooth muscle cells.
The response of rat aortic smooth muscle cells to all three isoforms of platelet-derived growth factor (PDGF) was studied. 5,000 binding sites/cell were estimated for rPDGF-AA (Kd 0.22 nM), 45,000 for rPDGF-AB and (Kd 0.4 nM), and 31,000 for rPDGF-BB (Kd 0.29 nM). rPDGF-AB and -BB stimulated effectively [3H]thymidine incorporation, inositol 1,4,5-trisphosphate release, diacylglycerol productions, [Ca2+]i increase, and pHi changes at concentration in the range from 3 to 10 ng/ml. The extent of DNA synthesis stimulated by rPDGF-AA varied considerably, and in all cases higher concentrations than 10 ng/ml were required. rPDGF-AA did not stimulate inositol-1,4,5-trisphosphate release, [Ca2+]i increase or pHi changes but induced the production of diacylglycerol, although with a different kinetic compared with that observed with rPDGF-AB or -BB. Apparently rPDGF-AA acts via a different mechanism, generating diacylglycerol without the release of inositol-1,4,5-trisphosphate.
Sachinidis
A
A
Department of Medicine, University of Zürich, Switzerland.
Locher
R
R
Vetter
W
W
Tatje
D
D
Hoppe
J
J
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D004075:Diglycerides / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007536:Isomerism; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor; D011994:Recombinant Proteins / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D004075:Diglycerides; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D017479:Receptors, Platelet-Derived Growth Factor; D002118:Calcium; D013936:Thymidine