Effects of PAF and PAF antagonists on the shape of venous endothelial cells in vitro.

Three platelet-activating factor (PAF) antagonists were tested for their ability to prevent or reduce PAF-induced shape changes of large vein endothelial cells in vitro. BN52021 had a significant protective action at concentrations of 1 microM and 0.1 microM, but at 100 microM had a damaging effect of its own. CV3988 (0.1 microM and 1 microM) and L652,731 (20 microM) did not reduce the responses to PAF, and at higher concentrations (CV3988 10 microM and 100 microM, L652,731 100 microM) both compounds alone caused significant changes of shape. BN52021 (0.1 microM) was also effective against leukotriene (LT) C4, at 1 microM against bradykinin and LTE4, and at 10 microM against LTD4 and the calcium ionophore A23187. BN52021 (10 microM) was ineffective against shape changes induced by histamine, prostaglandin (PG) E2 and lysophosphatidylcholine (LPC). Neither indomethacin (100 microM) nor verapamil (20 microM) altered the response to PAF. Using electron spin resonance (ESR) spectrometry it was shown that the damaging effects of LPC and CV3988 may be due partly to their detergent properties. It is suggested that the mechanism by which PAF alters the shape of large vein endothelial cells is primarily receptor mediated.