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Platelet-activating factor biosynthesis in rat vascular smooth muscle cells
P R Tomlinson1, K Croft, T Harris
1Microsurgery Research Centre, St. Vincent's Hospital, Fitzroy, Vic., Australia.
Journal of Vascular Research
|May 1, 1994
Summary
Vascular smooth muscle cells produce platelet-activating factor (PAF), but it does not appear to mediate endothelin-1
Area of Science:
- Vascular Biology
- Cell Signaling
- Pharmacology
Background:
- Platelet-activating factor (PAF) receptor antagonists show protective effects against endothelin-1-induced cardiovascular collapse in rats.
- Vascular smooth muscle cells' capacity to produce PAF and its functional roles require investigation.
- Understanding PAF's role in vascular smooth muscle is crucial for cardiovascular research.
Purpose of the Study:
- To determine if rat cultured vascular smooth muscle cells produce PAF.
- To evaluate the functional roles of PAF in these cells, particularly in response to vasoactive peptides.
- To investigate PAF's involvement in endothelin-1-induced cellular responses.
Main Methods:
- Stimulation of rat vascular smooth muscle cells with adenosine triphosphate and vasoactive peptides (endothelin-1, angiotensin II, arginine vasopressin).
- Measurement of PAF levels in cell extracts using bioassay and confirmation by Gas Chromatography-Mass Spectrometry (GC/MS).
- Assessment of intracellular calcium changes and [3H]-thymidine incorporation in response to exogenous PAF, endothelin-1, and fetal calf serum, with and without WEB 2086 (a PAF receptor antagonist).
Main Results:
- Adenosine triphosphate and vasoactive peptides increased intracellular PAF levels in rat vascular smooth muscle cells.
- PAF was produced and retained intracellularly, not detected in cell supernatants.
- Exogenous PAF increased intracellular calcium, but endothelin-1-induced calcium increases were not inhibited by WEB 2086, suggesting endogenous PAF is not involved.
- WEB 2086 partially inhibited serum-induced [3H]-thymidine incorporation but did not affect serum-induced cell number increases.
Conclusions:
- Cultured rat vascular smooth muscle cells produce and retain PAF.
- Endogenous PAF is unlikely to mediate endothelin-1-induced intracellular calcium increases in these cells.
- PAF's role in proliferation signaling in vascular smooth muscle cells appears limited.