Effect of platelet activating factor antagonists on cultured rat mesangial cells

Platelet activating factor (PAF; 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a lipid mediator of inflammation produced by inflammatory cells and also by renal glomerular mesangial cells. PAF may play a role in glomerular function and disease. Previously the authors reported that glomerular mesangial cells respond to PAF by increasing prostaglandin E2 (PGE2) synthesis and by cell contraction. This paper examines the specificity of BN52021, SRI 63-072 and kadsurenone on the effects of PAF on cultured rat glomerular mesangial cells. Both BN52021 and SRI 63-072 specifically decreased PAF (1 X 10(-6) M)-stimulated PGE2 production in a dose-dependent fashion (10(-7)-10(-5) M) without affecting the stimulation by angiotensin II (AII) or the calcium ionophore A23187. Kadsurenone also decreased PAF-stimulated PGE2 production, but in a less specific manner, as it also decreased AII- and A23187-stimulated PGE2 production. In order to examine the site of antagonism of PAF-induced PGE2 synthesis by BN52021 and SRI 63-072, the authors prelabeled cells with [14C]arachidonic acid. Both agents diminished the release of [14C]arachidonate from these prelabeled cells in response to PAF in a dose-dependent fashion, though not decreasing release in response to AII or A23187, indicating that they blocked the effect of PAF on phospholipase activation, consistent with receptor blocking activity. BN52021 and SRI 63-072 also inhibited PAF-induced contraction of cultured mesangial cells without an effect on basal tone of the cells or the contractile response to AII.(ABSTRACT TRUNCATED AT 250 WORDS)