Species dependence for binding of small molecule agonist and antagonists to the C5a receptor on polymorphonuclear leukocytes

This study investigated the receptor binding affinities of a C5a agonist an d cyclic antagonists for polymorphonuclear leukocytes (PMNs) isolated from human, sheep, pig, dog, rabbit, guinea pig, rat and mouse. The affinities o f the two small molecule antagonists, F-[OPdChaWR] and AcF-[OPdChaWR], and the agonist, YSFKPMPLaR, revealed large differences in C5a receptor (C5aR) affinities between species. The antagonists bound to human, rat and dog PMN s with similar high affinities, but with lower affinities to PMNs from all other species. The C5a agonist also bound with varying affinities between s pecies, but showed a different affinity profile to the antagonists. In cont rast, recombinant human C5a had similar affinity for PMNs of all species in vestigated. The low correlation between the affinities of the antagonists a nd the agonist between species either suggests that different receptor resi dues are important for distinguishing between agonist/antagonist binding, o r that the agonist and antagonist peptides bind to two distinct sites withi n the C5aR.