CV 6209 IS A NON‐COMPETITIVE ANTAGONIST OF PLATELET‐ACTIVATING FACTOR RECEPTORS ON GUINEA‐PIG RESIDENT PERITONEAL MACROPHAGES

SUMMARY 1. The characteristics of antagonism of platelet‐activating factor (Paf) receptors by the phospholipid Paf analogue, CV 6209, were studied in rabbit platelets and polymorphonuclear leucocytes (PMN) and in guinea‐pig macrophages. 2. Paf‐induced aggregation of PMN or platelets was antagonized in a competitive and specific manner by CV 6209 with no detectable difference between the p A 2 values (approximately 9.5). 3. The specificity of CV 6209 (1–100 nmol/L) for Paf receptors in platelets and PMN was indicated by a lack of effect on A23187 (10 μmol/L) or fMLP (1 μmol/L) induced aggregation, respectively. 4. CV 6209 (1–100 nmol/L) was also a potent antagonist of Paf‐induced prostacyclin (PGI 2 ) generation by guinea‐pig peritoneal macrophages. However, CV 6209 caused significant depression of the maximum response to Paf and a non‐parallel shift in the concentration‐response curve indicating a non‐competitive type antagonism. 5. PGI 2 generation induced by the ionophore A23187 was unaffected by CV 6209 (up to 100 nmol/L) whereas basal PGI 2 production by macrophages was reduced by lower concentrations (10–100 nmol/L). These observations are not consistent with a direct effect of CV 6209 on the enzymes involved in PGI2 synthesis but do suggest that endogenous Paf regulates basal PGI 2 generation. 6. The non‐competitive antagonism of guinea‐pig macrophage Paf receptors gives further support to the contention that these receptors are distinct from those mediating aggregation of platelets and PMN,