1. In isolated guinea-pig bronchial preparations the selective endothelin ET(B) agonist, IRL 1620 caused a concentration-dependent contraction. The pD2 value (7.16 ± 0.09, n = 6) was significantly increased in the presence of peptidase inhibitors (thiorfan 1 μM, captopril 1 μM, bestatin 1 μM) (pD2 = 7.75 ± 0.09, n = 6). Indomethacin (5 μM) did not appear to influence the ET(B)-agonist pD2 value (6.92 + 0.11, n = 6) but potentiated its maximal response significantly (67.23 ± 4.81% vs. 53.37 ± 4.80%). 2. The concentration-response curve for the contractile response to IRL 1620 (pD2 = 7.83 ± 0.01, n = 16) was reproducible, although not completely, since the second curve to this selective ET(B) agonist was shifted significantly to the right (pD2 = 7.34 ± 0.09, n = 16) and a decrease in the maximal response was observed (20.0 ± 2.0%). 3. BQ 788, a selective antagonist for ET(B) receptors, employed in concentrations ranging from 1.5 to 150 nM, caused a dose-dependent shift to the right of the concentration-response curve to IRL 1620, with a pIC50 value of 8.11 ± 0.03; this action was not influenced by adding enzyme inhibitors (pIC50 = 8.17 ± 0.29). 4. Our data show that IRL 1620 undergoes a hydrolytic metabolism in guinea-pig bronchial preparations, which could influence the calculation of the pD2. Pretreatment of the tissue with peptidase inhibitors and indomethacin is consequently significant in the evaluation of IRL 1620 activity, while it does not influence the action of the antagonist, BQ 788.

Role of peptidase and cyclooxygenase inhibitors in the guinea-pig bronchial response to the synthetic endothelin ET(B) agonist IRL 1620 and antagonist BQ-788

NIERI, PAOLA;LENZI, PAOLA;BRESCHI, MARIA CRISTINA
1999

Abstract

1. In isolated guinea-pig bronchial preparations the selective endothelin ET(B) agonist, IRL 1620 caused a concentration-dependent contraction. The pD2 value (7.16 ± 0.09, n = 6) was significantly increased in the presence of peptidase inhibitors (thiorfan 1 μM, captopril 1 μM, bestatin 1 μM) (pD2 = 7.75 ± 0.09, n = 6). Indomethacin (5 μM) did not appear to influence the ET(B)-agonist pD2 value (6.92 + 0.11, n = 6) but potentiated its maximal response significantly (67.23 ± 4.81% vs. 53.37 ± 4.80%). 2. The concentration-response curve for the contractile response to IRL 1620 (pD2 = 7.83 ± 0.01, n = 16) was reproducible, although not completely, since the second curve to this selective ET(B) agonist was shifted significantly to the right (pD2 = 7.34 ± 0.09, n = 16) and a decrease in the maximal response was observed (20.0 ± 2.0%). 3. BQ 788, a selective antagonist for ET(B) receptors, employed in concentrations ranging from 1.5 to 150 nM, caused a dose-dependent shift to the right of the concentration-response curve to IRL 1620, with a pIC50 value of 8.11 ± 0.03; this action was not influenced by adding enzyme inhibitors (pIC50 = 8.17 ± 0.29). 4. Our data show that IRL 1620 undergoes a hydrolytic metabolism in guinea-pig bronchial preparations, which could influence the calculation of the pD2. Pretreatment of the tissue with peptidase inhibitors and indomethacin is consequently significant in the evaluation of IRL 1620 activity, while it does not influence the action of the antagonist, BQ 788.
Lazzeri, N; Nieri, Paola; Lenzi, Paola; Ratti, C; Breschi, MARIA CRISTINA
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/203487
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 0
  • ???jsp.display-item.citation.isi??? ND
social impact