Functional characterization and m-RNA expression of 5-HT receptors mediating contraction in human umbilical artery.

1 5-HT(1)-like and 5-HT(2) receptors have both been described to mediate contractions to 5-HT in the human umbilical artery (HUA). However, the nature of the 5-HT receptor subtypes is unknown. 2 In isometric force studies with ring preparations of HUA alpha-methyl-5-hydroxytryptamine (alpha-Me-5-HT) and 5-hydroxytryptamine (5-HT) contracted HUA with pED(50) values of 8.04 and 7.74, respectively. In the presence of a subthreshold concentration of another vasoconstrictor sumatriptan and 5-nonyloxytryptamine elicited concentration-dependent contractions with pEC(50) values of 7.21 and 7.67, respectively. 3 In the presence of the selective 5-HT(1B/D) receptor antagonist GR127935, contractile responses elicited by sumatriptan and 5-nonyloxytryptamine were competitively antagonized (pK(B) 9.01 and 9.02, respectively). In the experiments with 5-HT, GR127935 appeared to be non-competitive with shallow Schild plot slopes. The data were fitted with two linear regression lines and the calculated pK(B) of the high affinity component (8.90) was comparable to that expected for GR127935 at the 5-HT(1B/1D) receptor. 4 Several 5-HT(2) selective receptor antagonists (spiperone, cyproheptadine, pirenperone) competitively inhibited responses to 5-HT. The selective 5-HT(2A) antagonist ketanserin against sumatriptan and 5-nonyloxytryptamine behaved as a weak antagonist while against 5-HT demonstrated a competitive antagonism (pK(B) 8.56). 5 Using specific primers for human 5-HT(1B), 5-HT(1D) and 5-HT(2A) receptor genes, the reverse transcriptase-polymerase chain reaction revealed mRNA expression of 5-HT(1B) and 5-HT(2A) receptors in the HUA. 6 The results suggest that the HUA has a functional population of 5-HT(1B) and 5-HT(2A) receptor subtypes which are involved in the contractile response to 5-HT. Contractions mediated by 5-HT(1B) receptors can be 'uncovered' by exposure to other vasoactive agents.