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.
Rogines-Velo
María Pía
MP
Departamento de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Piso 9, CP 1121, Buenos Aires, Argentina.
Pelorosso
Facundo Germán
FG
Zold
Camila Lidia
CL
Brodsky
Paula Tamara
PT
Rothlin
Rodolfo Pedro
RP
D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000378:metabolism / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000378:metabolism / Q000494:pharmacology; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin