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Antagonism of platelet activating factor‐induced chemiluminescence in guinea‐pig peritoneal macrophages in differing states of activation
Author(s) -
Parnham Michael J.,
Bittner Christine,
Lambrecht Günter
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb12631.x
Subject(s) - guinea pig , antagonism , chemiluminescence , pharmacology , platelet , platelet activating factor , chemistry , immunology , microbiology and biotechnology , biology , medicine , endocrinology , biochemistry , receptor , organic chemistry
1 The effects of the platelet activating factor (Paf) antagonists alprazolam, BN 52021, kadsurenone, L 652,731 and SRI 63119 have been studied on Paf‐induced chemiluminescence (CL) of guinea‐pig, C. parvum ‐activated peritoneal macrophages in vitro.2 All antagonists produced a shift to the right in the dose‐response curve to Paf (0.001–10 μmol l −1 ). Schild plots for BN 52021, L 652,731, kadsurenone and SRI 63119 were linear, but only for BN 52021 and kadsurenone did the mean slope not differ significantly from unity. Mean pA 2 values for BN 52021 and kadsurenone were 6.60 ± 0.05 and 6.41 ± 0.14 (mean + s.e.mean) respectively. Calculation of IC 50 values for all antagonists (at 0.1 μmol l −1 Paf) gave an order of potency: L 652731 > kadsurenone ≥ BN 52021 > alprazolam > SRI 63119. 3 When individual pA 2 values for BN 52021 and kadsurenone were plotted against the maximal CL response to Paf of cell suspensions in the absence of antagonist (reflecting the degree of activation of the macrophages by the C. parvum ), it was found that the affinity of both antagonists for macrophage Paf receptors remained relatively constant irrespective of the activation state of the cells. 4 We conclude that activation of guinea‐pig peritoneal macrophages does not account for the increased affinity for macrophage Paf receptors previously observed for kadsurenone. Kadsurenone and BN 52021 presumably bind to a site on Paf receptors which is not affected by the activation process, while alprazolam and SRI 63119 are non‐specific antagonists. The reason for the difference between the competitive nature of kadsurenone and its structural analogue L 652,731 is unclear.