Molecular cloning and pharmacological characterization of the canine B1 and B2 bradykinin receptors

The dog is a valuable animal model in the study of the physiological role o f both the B1 and B2 bradykinin receptors, To more thoroughly characterize the pharmacological properties of the canine kinin receptors we isolated th e cDNA sequence encoding the B1 and B2 bradykinin receptor subtypes and ove rexpressed them in Chinese hamster ovary (CHO) cells. The cDNA sequence of the canine B1 bradykinin receptor encodes a protein comprised of 350 amino acids that is 76% identical to the human B1 bradykinin receptor. The cDNA s equence of the canine B2 bradykinin receptor encodes a protein of 392 amino acids that is 81% identical to the human B2 bradykinin receptor. The amino acid sequence of the canine B1 and B2 receptors are 35% identical. Pharmac ological studies of the cloned receptors revealed that the agonist affinity of the dog B1 receptor is similar to the rodent B1 receptors, and differs from the human form in that there is no preference for the presence of the N-terminal Lys residue of [des-Arg(10)]lys-bradykinin. Significantly, the B 1 receptor antagonist [des-Arg(9),Leu(8)]BK behaves as partial agonist on t he cloned dog B1 receptor. The dog B2 receptor exhibits the 'classical' pha rmacological properties of this receptor subtype.