Antiproliferative effect of UTP on human arterial and venous smooth muscle cells.
We have investigated the hypothesis that responses associated with proliferation are regulated by extracellular nucleotides such as ATP and UTP in cultured human vascular smooth muscle cells (VSMC) derived from internal mammary artery (IMA) and saphenous vein (SV). Platelet-derived growth factor (PDGF), ATP, and UTP each generated an increase in cytosolic free Ca(2+) concentration ([Ca(2+)](i)) in both IMA- and SV-derived cells in the absence of detectable inositol 1,4,5-trisphosphate production. ATP alone had no effect on [(3)H]thymidine incorporation into DNA, but with a submaximal concentration of PDGF it raised [(3)H]thymidine incorporation in SV- but not IMA-derived cells. UTP alone also was without effect on [(3)H]thymidine incorporation or cell number. However, in both SV- and IMA-derived cells, UTP reduced the PDGF-stimulated [(3)H]thymidine response and PDGF-stimulated cell proliferation. This cannot be explained by an inhibitory effect on the p42/p44 mitogen-activated protein kinase (MAPK) cascade, since this response to PDGF was not attenuated by UTP. We conclude that, in human VSMC of both arterial and venous origin, UTP acts as an anti-proliferative regulator.
White
P J
PJ
Cell Signalling Laboratory, Department of Biological Sciences, De Montfort University, Leicester LE1 9BH.
Kumari
R
R
Porter
K E
KE
London
N J
NJ
Ng
L L
LL
Boarder
M R
MR
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008323:Mammary Arteries / Q000166:cytology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000502:physiology; D058472:Receptors, Purinergic P2Y1; D012501:Saphenous Vein / Q000166:cytology*; D013498:Suramin / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism / Q000494:pharmacology; D014316:Tritium; D010738:Type C Phospholipases / Q000378:metabolism; D014544:Uridine Triphosphate / Q000494:pharmacology*
D000970:Antineoplastic Agents; C546382:P2RY1 protein, human; D010975:Platelet Aggregation Inhibitors; D010982:Platelet-Derived Growth Factor; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D014316:Tritium; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D013498:Suramin; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D010738:Type C Phospholipases; D002118:Calcium; D014544:Uridine Triphosphate; D013936:Thymidine