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


Autoria(s): Woodruff, Trent M.; Strachan, Anna J.; Sanderson, Sam D.; Monk, Peter N.; Wong, Allan K.; Fairlie, David P.; Taylor, Stephen M.
Contribuinte(s)

B. N. Cronstein

Data(s)

01/06/2001

Resumo

This study investigated the receptor binding affinities of a C5a agonist and cyclic antagonists for polymorphonuclear leukocytes (PMNs) isolated from human, sheep, pig, dog, rabbit, guinea pig, rat and mouse. The affinities of 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 PMNs with similar high affinities, but with lower affinities to PMNs from all other species. The C5a agonist also bound with varying affinities between species, but showed a different affinity profile to the antagonists. In contrast, recombinant human C5a had similar affinity for PMNs of all species investigated. The low correlation between the affinities of the antagonists and the agonist between species either suggests that different receptor residues are important for distinguishing between agonist/antagonist binding, or that the agonist and antagonist peptides bind to two distinct sites within the C5aR.

Identificador

http://espace.library.uq.edu.au/view/UQ:60768

Idioma(s)

eng

Publicador

New York

Palavras-Chave #Cell Biology #Immunology #C5a Antagonist #C5a Agonist #Leukocytes #Protein-coupled Receptors #Anaphylatoxin Receptor #Pharmacological Characterization #Cloning #Terminus #Analogs #Region #Rat #Activation #Expression #C1 #06 Biological Sciences
Tipo

Journal Article