Article date: September 1999
By: Dimcho R Bachvarov, Steeve Houle, Magdalena Bachvarova, Johanne Bouthillier, Serge A St‐Pierre, Yoshihiro Fukuoka, Julia A Ember, François Marceau, in Volume 128, Issue 2, pages 321-326
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 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.
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).
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 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.
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
DOI: 10.1038/sj.bjp.0702812
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