Characterization of 5-HT receptor subtypes mediating contraction in human umbilical vein. 2. Evidence of involvement of 5-HT1B receptors using functional studies.

Previous studies have shown that a heterogeneous 5-HT receptor population may be involved in vasoconstrictor actions of 5-HT in human umbilical vein (HUV). The aim of the present study was to evaluate whether the 5-HT(1B/1D) receptor subtype mediates contraction in this tissue. 5-HT(1B/1D)-mediated responses can be enhanced or unmasked after exposure to threshold or sub-threshold KCl concentrations. In HUV rings, when 5-HT, alpha-Me-5HT or bradykinin concentration-response curves (CRC) were generated in the presence or absence of sub-threshold concentrations of KCl, there were not significant differences between the control and the treated rings. On the other hand, sumatriptan, the classic selective 5-HT(1B/1D) receptor agonist, produced a concentration-related contraction that was potentiated in the presence of sub-threshold KCl concentration. In addition, L-694,247, the novel selective 5-HT(1B/1D) receptor agonist, displayed a concentration-dependent contraction with high potency in HUV. The presence of sub-threshold concentrations of KCl produced a marked leftward shift of its CRCs.GR-55562, a 5-HT(1B/1D)-selective antagonist, competitively blocked sumatriptan CRCs with an estimated p A(2) of 8.00 and a slope not different from unity. Likewise, SB-216641, a selective 5-HT(1B) antagonist, produced a parallel rightward shift of sumatriptan CRCs in HUV. The Schild analysis yielded a p A(2) of 9.29, with a slope not different from unity. In addition, L-694,247 contractile responses were competitively blocked by SB-216641 with an estimated p A(2) value of 9.12 and a Schild slope not different from unity. On the other hand, ketanserin behaved as a weak antagonist of L-694,247-induced responses, yielding a calculated p A(2) value of 6.40. In summary, the results obtained in this study support that the 5-HT(1B) receptor subtype is involved in vasoconstrictor responses in HUV.