Cloning and preliminary pharmacological characterization of the anaphylatoxin C5a receptor in the rabbit.
1 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. 2 The rabbit C5a receptor stably expressed in RBL cells binds human 125I-C5a (2 nM). 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. 3 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. 4 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).
Bachvarov
D R
DR
Centre Hospitalier Universitaire de Québec, Centre de recherche, Pavillon l'Hôtel-Dieu de Québec, 11 Côte-du-Palais, Québec (Québec), G1R 2J6 Canada. dimchob@rsvs.ulaval.ca
Houle
S
S
Bachvarova
M
M
Bouthillier
J
J
St-Pierre
S A
SA
Fukuoka
Y
Y
Ember
J A
JA
Marceau
F
F
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics*; D001483:Base Sequence; D001667:Binding, Competitive / Q000187:drug effects; D001808:Blood Vessels / Q000378:metabolism; D003001:Cloning, Molecular; D015936:Complement C5a / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects; D011817:Rabbits; D011869:Radioligand Assay; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics*; D011994:Recombinant Proteins / Q000494:pharmacology; D014162:Transfection
D015703:Antigens, CD; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D011994:Recombinant Proteins; D015936:Complement C5a