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 t o be 79.5% identical to the human homologue, the highest degree of similari ty found so far in nonprimate laboratory animals. 2 The rabbit C5a receptor stably expressed in RBL cells binds human I-125-C 5a (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 a ffinity 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 art ery; 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 pres ervation degree of sequence and pharmacologic properties relative to the hu man ortholog receptor, thus defining a set of molecular tools for the inves tigation of the role of C5a in physiologic and pathologic models based on t he rabbit (e.g. atherosclerosis, inflammation).