Role of the 5-HT1D receptor in mediating the response of the human umbilical artery (HUA) to 5-HT
5-Hydroxytryptamine (5-HT) is a potent vasoconstrictor of the HUA and contraction is mediated via 5-HTi-like and 5-HT2 receptors. In the present study we have evaluated the effects of the selective 5-HT1D receptor agonists sumatriptan (Sum) and nonyloxytryptamine (NOT), and the antagonist GR 127935. Ring segments of the HUA were mounted in the organ chambers for the recording of change in isometric tension. Concentration-response curves (CRCs) to 5-MT, Sum and NOT were obtained. However, Sum- and NOT-induced contractions were observed only in tissues precontracted by threshold concentrations of KC1. The pEC50 values for 5-MT, Sum and NOT were 7.38 ±0.15, 7.16 ±0.01, and 7.92 ±0.12, respectively, with the Emax values (mean ±SE) not significantly different. The effect of the 5-HT1D selective antagonist, GR 127935 on 5-HT-, Sumand NOT-induced contractions of the HUA was also examined. Preincubation with GR 127935 (1-100 nM, n=5-8) for l h evoked a parallel rightward displacement of the CRC to agonist with no alteration of the maximum response. Schild analysis gave an apparent pA2 values for GR 127935 with 5-HT, Sum and NOT of 8.56 ±0.22, 9.02 ±0.40 and 9.64 ±0.80, respectively with slopes not different from unity. These data indicate the involvement of 5-HT]D receptor subtype in 5-HT-mediated contraction of the HUA.