Platelet activating factor biosynthesis in rat vascular smooth muscle cells

P.R. Tomlinson, Kevin Croft, T. Harris, A.G. Stewart

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The ability of platelet-activating factor (PAF) receptor antagonists to protect rats from the cardiovascular collapse induced by large doses of endothelin 1 led us to examine the capacity of rat cultured vascular smooth muscle cells to produce PAF and also to evaluate its potential functional roles in this cell type. Adenosine triphosphate and the vasoactive peptides, endothelin 1, angiotensin II, and arginine vasopressin, each elicited an increase in the PAF level in extracts of rat cultured vascular smooth muscle cells as determined by bioassay. PAF was not detectable (above 20 fmol/mg protein) in the supernatants of these cells. The identity of the bioactivity as PAF was confirmed by GC/MS which indicated that more than 80% of the PAF was 1-O-hexadecyl-2-acetyl-3-sn-glyceryl-phosphorylcholine. Exogenous PAF (100 nM) elicited increases in intracellular calcium that were inhibited by WEB 2086 (10 mu M). Endothelin 1, at a concentration which stimulated PAF synthesis, (1 nM), elicited increases in intracellular calcium levels that were not inhibited by WEB 2086 (10 mu M). Thus, endogenous PAF is unlikely to be involved in the endothelin-1-induced calcium increases. Although WEB 2086 (3-100 mu M) inhibited concentration dependently fetal calf serum (10% v/v) induced [H-3]-thymidine incorporation, reaching a maximum effect at 30 mu M of 40-50% reduction, in parallel experiments WEB 2086 had no effect on serum-induced increases in cell numbers. We conclude that PAF is produced and retained by cultured rat vascular smooth muscle and that it is unlikely to contribute to the signaling of increases in intracellular calcium or proliferation.
Original languageEnglish
Pages (from-to)144-152
JournalJournal of Vascular Research
Volume31
DOIs
Publication statusPublished - 1994

Fingerprint Dive into the research topics of 'Platelet activating factor biosynthesis in rat vascular smooth muscle cells'. Together they form a unique fingerprint.

Cite this