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Cloning and preliminary pharmacological characterization of the anaphylatoxin C5a receptor in the rabbit
Author(s) -
Bachvarov Dimcho R,
Houle Steeve,
Bachvarova Magdalena,
Bouthillier Johanne,
StPierre Serge A,
Fukuoka Yoshihiro,
Ember Julia A,
Marceau François
Publication year - 1999
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 - 10.1038/sj.bjp.0702812
Subject(s) - c5a receptor , anaphylatoxin , receptor , in vivo , potency , biology , microbiology and biotechnology , pharmacology , in vitro , biochemistry , immunology , antibody , complement system , genetics
The rabbit receptor for C5a was cloned from a genomic library and found to be 79.5% identical to the human homologue, the highest degree of similarity found so far in nonprimate laboratory animals. The rabbit C5a receptor stably expressed in RBL cells binds human 125 I‐C5a (2 n M ). Unlabelled C5a and the C‐terminal analogue N‐acetyl‐Tyr‐Ser‐Phe‐Lys‐Pro‐Met‐Pro‐Leu‐D‐Ala‐Arg (Ac‐YSFKPMPLaR) were found to be competitors of that binding, the peptide analogue retaining approximately 0.1% of the affinity of human C5a. The order of potency human C5a>Ac‐YSFKPMPLaR was conserved in bioassays based on rabbits (relaxation of the isolated portal vein and pulmonary artery; acute in vivo neutropenia), but with a decreasing potency gap between the two compounds, a likely consequence of the resistance to peptidases of the analogue. The molecular definition of the rabbit C5a receptor evidenced a high preservation degree of sequence and pharmacologic properties relative to the human ortholog receptor, thus defining a set of molecular tools for the investigation of the role of C5a in physiologic and pathologic models based on the rabbit (e.g. atherosclerosis, inflammation).British Journal of Pharmacology (1999) 128 , 321–326; doi: 10.1038/sj.bjp.0702812