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 (C16-PAF, C18-PAF; 0.000001 to 1 mumol/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 mumol/L) did not influence the concentration-response curve of either the beta-adrenoceptor agonist isoprenaline (ISO, 0.0001 to 1 mumol/L) or the m-cholinoceptor agonist carbachol (CARB, 0.0001 to 10 mumol/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 EC50 values--of both isoprenaline and carbachol were identical with and without pretreatment with PAF (0.2 mumol/L). PAF at concentrations of 0.000001 to 10 mumol/L exerted no effect on force of contraction either precontracted (prostaglandin F2 alpha, 0.3 mumol/L) or unprecontracted in human coronary artery rings. Histamine (0.01 to 100 mumol/L) and noradrenaline (0.001 to 30 mumol/L) initiated concentration-dependent contraction in human coronary artery rings (EC50: histamine, 1.86 mumol/L; noradrenaline, 0.69 mumol/L). At lower concentrations (PAF, 0.01 mumol/L) PAF produced complete aggregation of human platelets. In human platelet membranes and lung membranes, 3H-WEB 2086 exhibited saturable high-affinity binding (KD 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 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).

journal_name

Am Heart J

journal_title

American heart journal

authors

Schwinger RH,Böhm M,La Rosée K,Erdmann E

doi

10.1016/0002-8703(92)90593-k

subject

Has Abstract

pub_date

1992-08-01 00:00:00

pages

320-30

issue

2

eissn

0002-8703

issn

1097-6744

pii

0002-8703(92)90593-K

journal_volume

124

pub_type

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