Document Detail

Characterization of bradykinin B(2) receptor antagonists in human and rat urinary bladder.
MedLine Citation:
PMID:  10666510     Owner:  NLM     Status:  MEDLINE    
The effect of three selective bradykinin B(2) receptor antagonists, MEN11270 (H-DArg-Arg-Pro-Hyp-Gly-Thi-c(Dab-DTic-Oic-Arg)c(7gamma-1 0alpha)), Icatibant (H-DArg-Arg-Pro-Hyp-Gly-Thi-Ser-DTic-Oic-Arg-OH), and FR173567 ((E)-3-(6-acetamido-3-pyridyl)-N-[N-[2, 4-dichloro-3-[(2-methyl-8-quinolinyl) oxymethyl] phenyl]-N-methylaminocarbonylmethyl]acrylamide) was evaluated in the human and rat urinary bladder in vitro and in vivo in anaesthetized rats. Bradykinin evoked a concentration-dependent contraction of human (pD(2)=7.2) and rat (pD(2)=7.7) detrusor muscle strips. In human preparations, all the antagonists tested produced a rightward-shift in the concentration-response curve for bradykinin. Schild plot analysis yielded pK(B) values of 8.4, 8.4 and 8.6 for MEN11270, Icatibant, and FR173567, respectively. In the rat preparations the three antagonists (at 100 nM concentration), produced a shift to the right which gave apparent pA(2) values of 8. 2, 8.0 and 8.1 for MEN11270, Icatibant, and FR173567, respectively. In anaesthetized rats, both MEN11270 and Icatibant (1-10 nmol/kg i.v. ) dose dependently reduced the bradykinin (100 nmol/kg i.v.)-induced urinary bladder contraction, their effect being prompt and long-lasting. In contrast, FR173567 (100 nmol/kg i.v.) produced a partial and short-lasting inhibition of bradykinin-induced bladder contractions. The present findings indicate that all the antagonists tested recognize with similar potencies the bradykinin B(2) receptors expressed in the detrusor muscle of both humans and rats. MEN11270 and Icatibant possess a higher potency and longer duration of action in vivo than FR173657, suggesting that the activity of this non-peptide antagonist in vivo is hampered by factors unrelated to its affinity for bradykinin B(2) receptors.
S Meini; R Patacchini; S Giuliani; M Lazzeri; D Turini; C A Maggi; A Lecci
Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  European journal of pharmacology     Volume:  388     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2000 Jan 
Date Detail:
Created Date:  2000-03-16     Completed Date:  2000-03-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  177-82     Citation Subset:  IM    
Pharmacology Department, Menarini Ricerche, via Rismondo 12 A, 50135, Florence, Italy.
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MeSH Terms
Anesthesia, Intravenous
Anesthetics, Intravenous
Bradykinin / analogs & derivatives*,  antagonists & inhibitors,  pharmacology
Middle Aged
Muscle Contraction / drug effects
Muscle, Smooth / drug effects
Oligopeptides / pharmacology*
Peptides, Cyclic / pharmacology*
Quinolines / pharmacology*
Rats, Wistar
Receptor, Bradykinin B2
Receptors, Bradykinin / antagonists & inhibitors*
Urinary Bladder / drug effects*
Reg. No./Substance:
0/Anesthetics, Intravenous; 0/FR 173657; 0/MEN 11270; 0/Oligopeptides; 0/Peptides, Cyclic; 0/Quinolines; 0/Receptor, Bradykinin B2; 0/Receptors, Bradykinin; 130308-48-4/icatibant; 51-79-6/Urethane; 58-82-2/Bradykinin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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