Existence of PAF receptors in human platelets and human lung tissue but not in the human myocardium

Abstract

The aim of this study was to investigate whether platelet-activating factor (PAF), PAF receptors, and PAF receptor-mediated effects in the human myocardium play a role in cardiac depression during anaphylaxis or septic shock. The effects of PAF, the biologically inactive derivative lyso-PAF, and the specific PAF antagonist WEB 2086 were studied in human myocardial tissue, in human coronary arteries, in human platelets, and in human lung tissue. PAF (C 16-PAF, C 18-PAF; 0.000001 to 1 μmol/L) had no effect on isometric force of contraction of electrically driven right atrial trabeculae (patients undergoing aortocoronary bypass surgery) and left ventricular papillary muscle strips (mitral valve replacement). PAF (0.2 μmol/L) did not influence the concentration-response curve of either the β-adrenoceptor agonist isoprenaline (ISO, 0.0001 to 1 μmol/L) or the m-cholinoceptor agonist carbachol (CARB, 0.0001 to 10 μmol/L). The effectiveness (ISO +4.7 ± 0.7 mN, PAF + ISO + 4.3 ± 0.44 mN, CARB −2.7 ± 1.06 mN; PAF + CARB −2.6 ± 0.52 mN) and the potency—as indicated by the EC 50 values—of both isoprenaline and carbachol were identical with and without pretreatment with PAF (0.2 μmol/L). PAF at concentrations of 0.000001 to 10 μmol/L exerted no effect on force of contraction either precontracted (prostaglandin F 2α, 0.3 μmol/L) or unprecontracted in human coronary artery rings. Histamine (0.01 to 100 μmol/L) and noradrenalin (0.001 to 30 μmol/L) initiated concentration-dependent contraction in human coronary artery rings (EC 50: histamine, 1.86 μmol/L; noradrenalin, 0.69 μmol/L). At lower concentrations (PAF, 0.01 μmol/L) PAF produced complete aggregation of human platelets. In human platelet membranes and lung membranes, 3H-WEB 2086 exhibited saturable high-affinity binding (K D 14.4 nmol/L and 14.3 nmol/L). The maximal binding capacity was 292 fmol/mg protein and 268 fmol/mg protein, respectively. In displacement experiments PAF (0.01 to 10000 nmol/L) and WEB 2086 (0.01 to 10000 nmol/L), but not lyso-PAF, completely displaced 3H-WEB 2086 from its binding sites on human platelet and lung membranes. In contrast, neither in left ventricular membranes nor in right atrial membranes was specific binding of 3H-WEB 2086 observed. These results suggest that there are neither specific PAF receptors nor direct PAF-mediated actions in human myocardial tissue or human coronary artery rings. The effects of PAF on myocardial function may be due to the activation of mediators (e.g., histamine).