Human Umbilical Vein: Involvement Of Cyclooxygenase-2 Pathway In Bradykinin B1 Receptor Sensitized Responses

ANDREA ERRASTI, VERÓNICA REY-ARES, FEDERICO DARAY, MARÍA ROGINES-VELO, SERGIO SARDI, CRISTINA PAZ, ERNESTO PODESTÁ, RODOLFO ROTHLIN

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY

Springer Berlin / Heidelberg

Lugar: Berlin / Heidelberg; Año: 2001 vol. 364 p. 149 - 156

0028-1298

Autores Andrea Errasti, Verónica Rey-Ares, Federico Daray, María Rogines-Velo, Sergio Sardi, Cristina Paz, Ernesto Podestá, Rodolfo Rothlin 1Departamento de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Piso 9, CP 1121 Buenos Aires, Argentina2Departamento de Bioquímica, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina Resumen In isolated human umbilical vein (HUV), the contractile response to des-Arg9-bradykinin (des-Arg9-BK), selective BK B1 receptor agonist, increases as a function of the incubation time. Here, we evaluated whether cyclooxygenase (COX) pathway is involved in BK B1-senzitized response obtained in 5-h incubated HUV rings. The effect of different concentrations of indomethacin, sodium salicylate, ibuprofen, meloxicam, lysine clonixinate or NS-398 administrated 30 min before concentration-response curves (CRC) was studied. All treatments produced a significant rightward shift of the CRC to des-Arg9-BK in a concentration-dependent manner, which provides pharmacological evidence that COX pathway is involved in the BK B1 responses. Moreover, in this tissue, the NS-398 pKb (5.2) observed suggests that COX-2 pathway is the most relevant. The strong correlation between published pIC50 for COX-2 and the NSAIDs´ pKbs estimated further supports the hypothesis that COX-2 metabolites are involved in BK B1 receptor-mediated responses. In other rings, indomethacin (30, 100 µmol/l) or NS-398 (10, 30 µmol/l) produced a significant rightward shift of the CRC to BK, selective BK B2 agonist, and its pKbs were similar to the values to inhibit BK B1 receptor responses, suggesting that COX-2 pathway also is involved in BK B2 receptor responses. Western blot analysis shows that COX-1 and COX-2 isoenzymes are present before and after 5-h in vitro incubation and apparently COX-2 does not suffer additional induction. Palabras clave Human umbilical vein, Cyclooxygenase-1, Cyclooxygenase-2, Bradykinin B 1 and B 2 receptors, Non-steroidal antiinflammatory drugs