THE AGONIST SELECTIVITY OF A MOUSE B-1 BRADYKININ RECEPTOR DIFFERS FROM HUMAN AND RABBIT B-1 RECEPTORS

A genomic clone encoding the mouse B-1 receptor was isolated by homolo gy to the human B-1 receptor cDNA. The deduced amino acid sequence of the mouse B-1 receptor is 72% identical to the human B-1 receptor and 73% identical to the rabbit B-1 receptor. Ligand binding studies of th e mouse B-1 receptor expressed in COS cells indicate that it has the p harmacological properties associated with the B-1 receptor subtype. Ho wever, the pharmacology of the mouse receptor is unique in that it pos sesses a 2-3-fold selectivity for the 'classical' B-1 agonist des-Arg( 9)BK over the agonist des-Arg(10)kallidin. In contrast, the human and rabbit B-1 receptors exhibit an approx. 2000- and 150-fold selectivity , respectively, for des-Arg(10)kallidin over des-Arg(9)BK. Thus relati ve to the human and rabbit B-1 receptors the mouse B-1 receptor has th e opposite selectivity for kinin agonists. The DNA sequence of the reg ion encoding bradykinin was determined for two different mouse kininog en cDNA clones, both encode the sequence Arg-BK. Antipeptide antibodie s directed against a C-terminal peptide of the human B-1 receptor were produced. Initial characterization of this antibody indicates that it detects specific bands by Western blot analyses that are present in m embranes prepared from COS cells transfected with the human B-1 recept or cDNA but not from mock transfected COS cells.