Characterisation of bradykinin B1 and B2 receptors using rat isolated vas deferens.
The actions of bradykinin and its metabolite des-Arg(9) bradykinin are mediated through activation of bradykinin B(2) and B(1) receptors, respectively. The aim of the present study was to characterize native bradykinin receptors focusing on induction and desensitization using rat isolated vas deferens. Tissues were mounted in organ baths for isometric recordings and neurogenically mediated contractions were evoked by electrical stimulation. Des-Arg(9) bradykinin enhanced the magnitude of the electrically evoked contractions and this effect (which was sensitive to blockade by the peptide bradykinin B(1) receptor selective antagonist B9858, Lys-Lys-(Hyp(3),Cpg(5),D-Tic(7),Cpg(8))des-Arg(9) bradykinin) was only observed following a pre-incubation period and was greatest following 5 h of pre-incubation. Bradykinin also potentiated neurogenically evoked contractions and this effect was sensitive to blockade by Hoe 140 (D-Arg(Hyp(3),Thi(5),D-Tic(7),Oic(8))bradykinin, a peptide bradykinin B(2) receptor antagonist) and was present without pre-incubation but was increased by pre-incubation and reached maximum at the 5-h incubation time point. Responses to bradykinin were larger than those to des-Arg(9) bradykinin. Bradykinin responses did not show desensitization on repeated agonist stimulation. These data confirm in rat isolated vas deferens bradykinin B(2), but not B(1), receptors are constitutively expressed, that both receptor populations are inducible and B(2) receptors do not exhibit desensitization.
Scott
Paul
P
Merck Sharp and Dohme Research Laboratories, Terlings Park, Neuroscience Research Centre, Eastwick Road, Harlow, Essex, CM20 2QR, UK.
Razzaque
Zerin
Z
Longmore
Jenny
J
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000819:agonists / Q000502:physiology*; D013997:Time Factors; D014649:Vas Deferens / Q000187:drug effects* / Q000502:physiology
C121350:B 9858; D065168:Bradykinin Receptor Antagonists; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; C024626:bradykinin, des-Arg(9)-; C065679:icatibant; D003000:Clonidine; D001920:Bradykinin; D011224:Prazosin