Specific receptor sites for 1-0-alkyl-2-0-acetyl-sn-glycero-3-phosphocholine (platelet activating factor) on rabbit platelet and guinea pig smooth muscle membranes

Abstract

By using tritiated 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine (3H-PAF), we have directly identified its specific binding sites on rabbit platelet plasma membranes. The equilibrium dissociation constant for 3H-PAF is 1.36 (+/- 0.05) X 10(-9) M at 0 degrees C. The number of binding sites is 1.61 (+/- 0.34) X 10(12)/mg of membrane, which corresponds to approximately 150-300 receptors/platelet (depending on membrane vesicle orientation). Binding of 3H-PAF to rabbit platelet plasma membrane is rapid (t1/2 less than 5 min at 0 degrees C) and reversible. For a series of PAF analogues, their affinity for the receptor sites parallels with their relative potency to induce platelet aggregation. PAF can cause contraction of smooth muscle of heart, parenchymal strip, trachea, and ileum. Specific PAF receptor binding was demonstrated with purified plasma membrane from several smooth muscles and from polymorphonuclear leukocytes but not from presumably PAF nonresponsive cells such as erythrocytes and alveolar macrophages. It is likely that the interaction of PAF with these binding sites initiates the specific responses of platelets, polymorphonuclear leukocytes, and smooth muscles.

Mechanisms of the coronary vascular effects of platelet‐activating factor in the rat perfused heart

“…1984;Piper & Stewart, 1986;Fiedler et al, 1987). However, not affect the the vasodilator effect, when observed, was not altered by FPL-)Opmol LTC4 55712 (Feuerstein et al, 1984;Fiedler et al, 1987 (Piper & Stewart, 1986; us to examine Man et al, 1990) ts, Specific binding of radiolabelled PAF was first demonn the coronary strated in platelets (Valone et al, 1982;Hwang et al, 1983) and subsequently demonstrated in a number of tissues (see review of Braquet et al, 1987). The binding of PAF showed the presence of high affinity sites, stereospecificity and saturation kinetics.…”

Increased hepatic platelet activating factor (PAF) and PAF receptors in carbon tetrachloride induced liver cirrhosis

“…42 In the present study, stellate cells from cirrhotic liver had a 2.6-fold increase in PAF receptor density and a 1.6-fold increase in PAF induced PGE 2 synthesis relative to control cells, matching the augmented sensitivity to PAF of the intact organ. The smooth muscle component of the hepatic vasculature may also contribute [51][52][53] to PAF induced increases in portal pressure.…”

Platelet‐activating factor mobilises intracellular calcium in vascular smooth muscle cells

“…Binding sites for PAF have been shown to be present on a number of cell types including platelets [12-141, neutrophils [15,16], guinea pig smooth muscle membranes [12] and lung tissue [ 171, suggesting that PAF exerts its effects via a specific extracellular receptor. Investigation of the postreceptor events intrinsic to PAF action has been carried out mainly in platelets where PAF can elevate the intracellular calcium level, [Ca'+]i, although it stimulates shape change even when [Ca*+]i is suppressed [18].…”

“…Hwang et al [12] have shown specific binding sites for PAF on several tissues, including rabbit ileal smooth muscle membranes, with a dissocation constant in the nanomolar range. Our findings support the view that these sites are functional receptors, the stimulation of which results in phospholipase C-mediated degradation of PtdInsPz and the subsequent production of InsPJ and 1,Zdiacylglycerol.…”