Human umbilical vein: involvement of cyclooxygenase-2 pathway in bradykinin B1 receptor-sensitized responses.
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-sensitized 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 micromol/l) or NS-398 (10, 30 micromol/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.
Errasti
A E
AE
Departamento de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Rey-Ares
V
V
Daray
F M
FM
Rogines-Velo
M P
MP
Sardi
S P
SP
Paz
C
C
Podestá
E J
EJ
Rothlin
R P
RP
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051546:Cyclooxygenase 2; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007527:Isoenzymes / Q000502:physiology*; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins; D009924:Organ Culture Techniques; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000819:agonists / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014471:Umbilical Veins / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; D008565:Membrane Proteins; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; C024626:bradykinin, des-Arg(9)-; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D001920:Bradykinin