The pharmacology of T-kinin and des-Arg(11)-T-kinin in primary cultures of rat bladder smooth muscle cells.
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.
Davis
Clare
C
Novartis Institute for Medical Sciences, 5 Gower Place, London WC1E 6BS, UK. clare.davis@pharma.novartis.com
Burgess
Gillian
G
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000819:agonists / Q000378:metabolism; D001743:Urinary Bladder / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D065168:Bradykinin Receptor Antagonists; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; C472345:des-arginine(11)-T-kinin, rat; C039065:T-kinin; D001920:Bradykinin; D002118:Calcium