5-hydroxytryptamine receptors mediating contraction in human small muscular pulmonary arteries: importance of the 5-HT1B receptor

Br J Pharmacol. 1999 Oct;128(3):730-4. doi: 10.1038/sj.bjp.0702841.


1. The 5-hydroxytryptamine (5-HT) receptors mediating vasoconstriction in isolated human small muscular pulmonary arteries (SMPAs) were determined using techniques of wire myography and reverse transcription-polymerase chain reaction (RT - PCR). 2. The agonists 5-HT, 5-carboxamidotryptamine (5-CT, unselective for 5-HT1 receptors) and sumatriptan (selective for 5-HT1B/D receptors) all caused contraction and were equipotent (pEC50s: 7.0+/-0.2, 7.1+/-0.3 and 6.7+/-0.1, respectively) suggesting the presence of a 5-HT1 receptor. 3. Ketanserin (5-HT2A-selective antagonist, 0.1 microM) inhibited 5-HT-induced contractions only at non-physiological/pathological concentrations of 5-HT (>0.1 microM) whilst GR55562 (5-HT1B/1D-selective antagonist, 1 microM) inhibited 5-HT-induced contractions at all concentrations of 5-HT (estimated pKB=7.7+/-0.2). SB-224289 (5-HT1B-selective antagonist, 0.2 microM) inhibited sumatriptan-induced contractions (estimated pKB=8.4+/-0.1) whilst these were unaffected by the 5-HT1D-selective antagonist BRL15572 (0.5 microM) suggesting that the 5-HT1B receptor mediates vasoconstriction in this vessel. 4. RT - PCR confirmed the presence of substantial amounts of mRNA for the 5-HT2A and 5-HT1B receptor subtypes in these arteries whilst only trace amounts of 5-HT1D receptor message were evident. 5. These findings suggest that a heterogeneous population of 5-HT2A and 5-HT1B receptors co-exist in human small muscular pulmonary arteries but that the 5-HT1B receptor mediates 5-HT-induced vasoconstriction at physiological and pathophysiological concentrations of 5-HT. These results have important implications for the treatment of pulmonary hypertension in which the 5-HT1B receptor may provide a novel and potentially important therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Benzamides / pharmacology
  • Biphenyl Compounds / pharmacology
  • DNA Primers
  • Humans
  • Ketanserin / pharmacology
  • Muscle Contraction / physiology
  • Piperazines / pharmacology
  • Piperidones / pharmacology
  • Pulmonary Artery / drug effects
  • Pulmonary Artery / physiology*
  • Pyridines / pharmacology
  • Receptor, Serotonin, 5-HT1B
  • Receptors, Serotonin / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serotonin Antagonists / pharmacology
  • Spiro Compounds / pharmacology


  • Benzamides
  • Biphenyl Compounds
  • DNA Primers
  • HTR1B protein, human
  • Piperazines
  • Piperidones
  • Pyridines
  • Receptor, Serotonin, 5-HT1B
  • Receptors, Serotonin
  • SB 22489G
  • Serotonin Antagonists
  • Spiro Compounds
  • 3-(3-(dimethylamino)propyl)-4-hydroxy-N-(4-(4-pyridinyl)phenyl)benzamide
  • Ketanserin
  • BRL 15572