title: Differences in electromechanical coupling between bradykinin and the nonpeptide kinin B2 receptor agonist, FR 190997, in the circular muscle of guinea-pig colon.
abstract: We have compared the effect of bradykinin (BK) and the nonpeptide kinin B2 receptor agonist, FR 190997, in producing changes in membrane potential and tension in the circular muscle of guinea-pig colon by the sucrose gap technique. In the presence of atropine (1 microM), S-ketoprofen (3 microM) and apamin (0.1 microM), BK (1 microM for 20 s) induced a transient depolarization of the membrane with superimposed action potentials (spikes) and transient contraction. Nifedipine (1 microM) eliminated the spikes and markedly inhibited the BK-induced contractions. FR 190997 (3-10 microM for 20 s) induced a slowly developing sustained small depolarization associated with a slowly developing and sustained contraction but, contrary to BK, FR 190997 was unable to trigger spikes. Nifedipine had no effect on depolarization and contraction induced by FR 190997. In the presence of 1 microM nifedipine, the combined application of a blocker of receptor-operated cation channels, SKF 96365 (50 microM for 30 min), and of an inhibitor of sarcoplasmic reticulum calcium pump, cyclopiazonic acid (CPA 10 microM for 30 min), reduced the BK-induced depolarization and contraction by about 45%-60%. The same treatment induced about 40% reduction of the sustained contraction induced by FR 190997, whereas the concomitant depolarization was not significantly affected. The tyrosine kinase inhibitor genistein (40 microM for 20 min) had no effect on the BK- and FR 190997-induced depolarization and contraction in the presence of nifedipine. In radioligand binding experiments performed in membranes of colonic smooth muscle cells, both agonists displaced the [3H]BK specific binding with a pIC50 of 9.6 and 8.5 for BK and FR 190997, respectively. These findings indicate a substantial qualitative difference in mechanisms of excitation contraction coupling activated by BK and FR 190997 via B2 receptors in guinea-pig colon.
authors.affiliation: Pharmacology Department, Menarini Ricerche SpA, Florence, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Santicioli
authors.forename: R M
authors.initials: RM
authors.lastname: Catalioto
authors.forename: S
authors.initials: S
authors.lastname: Meini
authors.forename: C A
authors.initials: CA
authors.lastname: Maggi
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002478:Cells, Cultured; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D006168:Guinea Pigs; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology*; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000819:agonists* / Q000378:metabolism
chemical_list: C107104:FR 190997; D011804:Quinolines; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D001920:Bradykinin