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

Fina Lovren, Xiao Fang Li, Jonathan Lytton, Christopher Triggle

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

1. 5-HT1-like and 5-HT2 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 α-methyl-5-hydroxytryptamine (α-Me-5-HT) and 5-hydroxytryptamine (5-HT) contracted HUA with pED50 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 pEC50 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-HT2 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.

Original languageEnglish
Pages (from-to)1247-1255
Number of pages9
JournalBritish Journal of Pharmacology
Volume127
Issue number5
DOIs
Publication statusPublished - 1999
Externally publishedYes

Fingerprint

Umbilical Arteries
Serotonin Receptors
Serotonin
RNA
Receptor, Serotonin, 5-HT1B
Sumatriptan
Cyproheptadine
Ketanserin
Serotonin Antagonists
Vasoconstrictor Agents
Reverse Transcriptase Polymerase Chain Reaction
Linear Models

Keywords

  • 5-HT(1B) and 5-HT(2A) receptors
  • Human umbilical artery
  • Vasoconstriction, RT-PCR

ASJC Scopus subject areas

  • Pharmacology

Cite this

Functional characterization and m-RNA expression of 5-HT receptors mediating contraction in human umbilical artery. / Lovren, Fina; Li, Xiao Fang; Lytton, Jonathan; Triggle, Christopher.

In: British Journal of Pharmacology, Vol. 127, No. 5, 1999, p. 1247-1255.

Research output: Contribution to journalArticle

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N2 - 1. 5-HT1-like and 5-HT2 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 α-methyl-5-hydroxytryptamine (α-Me-5-HT) and 5-hydroxytryptamine (5-HT) contracted HUA with pED50 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 pEC50 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-HT2 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.

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