Characterisation of 5-HT receptors in human coronary arteries by molecular and pharmacological techniques

Eur J Pharmacol. 1999 May 7;372(1):49-56. doi: 10.1016/s0014-2999(99)00114-4.


5-Hydroxytryptamine (5-HT) can produce both vasoconstrictor and vasorelaxant effects in human coronary arteries and the response to 5-HT can be influenced by the presence of disease. The aim of the present study was to elucidate the 5-HT receptor subtypes responsible for mediating 5-HT-evoked contraction of human coronary arteries using pharmacological, molecular and immunocytochemical approaches. Normal human coronary arteries, with intact endothelium, were mounted in tissue baths, and the vascular responses to 5-HT and 5-HT receptor agonists were studied. The effects of 5-HT1 and 5-HT2 receptor antagonists on these responses were also studied. Expression of messenger ribonucleic acid (mRNA) encoding different 5-HT receptors in human coronary arteries, atrium, ventricle wall and epicardium was determined using reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot analysis. The expression of 5-HT1B or 5-HT1D receptor protein was studied using subtype selective antibodies and standard immunocytochemical techniques. The rank order of 5-HT receptor agonist potency in causing vasoconstriction was 5-carboxamido tryptamine, (5-CT) > zolmitriptan = BW183C91 (N10-desmethyl zolmitriptan) = alpha-methyl-5-hydroxytryptamine (alpha-CH3-5-HT) = 5-HT = sumatriptan > 2-methyl-5-hydroxytryptamine (2-CH3-5-HT) = 8-hydroxy-DPAT (8-OH-DPAT). Alpha-CH3-5-HT, 5-CT, 5-HT, zolmitriptan and BW 183C91 were significantly more potent (approximately 3-fold) than sumatriptan and 2-CH3-5-HT, which in turn were more potent than 8-OH-DPAT. Ketanserin and methiothepin (5-HT2 and 5-HT1 receptor antagonists, respectively) caused parallel rightward shifts of the concentration-effect curves to alpha-CH3-5-HT or 5-CT, respectively, without changing the maximum contractile response. In human coronary arteries, atrium. ventricle and epicardium. RT-PCR products corresponding to the human 5-HT2A, 5-HT1B and 5-HT1F receptors were expressed in high levels, mRNAs coding for 5-HT7, 5-HT1A and 5-HT1D receptors were only weakly expressed. No 5-HT1F receptor mRNA was detected. In coronary arteries there was a differential expression of 5-HT1B versus 5-HT1D receptor mRNAs, with 5-HT1B mRNAs being found in greater abundance. Dense 5-HT1B-immunoreactivity was detected on smooth muscle layer within coronary artery, however, 5-HT1D-immunoreactivity was not detected. It is concluded that 5-HT-evoked contraction of human coronary arteries is most probably mediated via the activation of both 5-HT1B and 5-HT2A receptors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Cardiovascular System / drug effects
  • Cardiovascular System / metabolism
  • Coronary Vessels / drug effects
  • Coronary Vessels / metabolism
  • Coronary Vessels / physiopathology*
  • Dose-Response Relationship, Drug
  • Gene Expression / drug effects
  • Humans
  • Immunohistochemistry
  • In Vitro Techniques
  • Ketanserin / pharmacology
  • Methiothepin / pharmacology
  • Oxazoles / pharmacology
  • Oxazolidinones*
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, Serotonin, 5-HT1B
  • Receptor, Serotonin, 5-HT1D
  • Receptors, Serotonin / analysis
  • Receptors, Serotonin / genetics
  • Receptors, Serotonin / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serotonin / analogs & derivatives
  • Serotonin / pharmacology
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Sumatriptan / pharmacology
  • Tissue Distribution
  • Tryptamines
  • Vasoconstriction / drug effects


  • HTR1B protein, human
  • Oxazoles
  • Oxazolidinones
  • RNA, Messenger
  • Receptor, Serotonin, 5-HT1B
  • Receptor, Serotonin, 5-HT1D
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Tryptamines
  • zolmitriptan
  • Serotonin
  • Methiothepin
  • 2-methyl-5-HT
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Sumatriptan
  • 5-carboxamidotryptamine
  • Ketanserin