The pharmacology of T-kinin and des-Arg 11-T-kinin in primary cultures of rat bladder smooth muscle cells

Abstract

T-kinin and its putative carboxypeptidase product des-Arg 11-T-kinin are members of the kinin family that are unique to the rat. Primary cultures of rat bladder smooth muscle cells were used to investigate the pharmacology of these peptides. Calcium imaging experiments showed that rat bladder smooth muscle cells responded to both bradykinin and des-Arg 9-bradykinin with an increase in [Ca 2+] i and responses to both agonists could be observed in the same cell. A more detailed pharmacological characterisation with a range of bradykinin receptor agonists and antagonists using 45Ca 2+ efflux confirmed the presence of both B 1 and B 2 bradykinin receptors. Using this cellular model, we confirm that T-kinin is a bradykinin B 2 receptor agonist and show for the first time that des-Arg 11-T-kinin is a potent and selective bradykinin B 1 receptor agonist. In addition, using cells expressing the cloned rat and human bradykinin B 2 receptors plus the Ca 2+-sensitive protein aequorin, T-kinin was shown to be selective for the rat over the human bradykinin B 2 receptor.