Ca2+-channel blockers inhibit the action of recombinant platelet-derived growth factor in vascular smooth muscle cells.
Human platelet-derived growth factor (PDGF) is mainly composed of two polypeptide chains (PDGF-AB). All three possible dimeric forms of PDGF--i.e., PDGF-AA, PDGF-BB and PDGF-AB--exist in nature. We have used two recombinant PDGF homodimers to determine the roles of each isoform in the activation of phosphatidylinositol turnover in vascular smooth muscle cells (VSMC) isolated from rat thoracic aorta, their mitogenic effect on VSMC, and their vasoconstrictor effect on intact strips of aortic vascular tissue. Three Ca2+-channel blockers, nifedipine, verapamil, and diltiazem, were used as antagonists for investigating the PDGF-dependent changes mediated by the homodimers. PDGF-BB had a greater efficacy than PDGF-AA on inositol 1,4,5-trisphosphate release, on the formation of diacylglycerol, and on Ca2+ mobilization, which was also associated with vasoconstrictor activity and effective mitogenicity. PDGF-AA, on the other hand, was more potent than PDGF-BB in stimulating protein kinase C. In all instances, the activation of the phosphatidylinositol turnover by the two homodimers was inhibited by the Ca2+-channel blockers.
Block
L H
LH
Department of Medicine, University of Freiburg, Federal Republic of Germany.
Emmons
L R
LR
Vogt
E
E
Sachinidis
A
A
Vetter
W
W
Hoppe
J
J
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D004110:Diltiazem / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D002118:Calcium