Differential classification of vascular smooth muscle and endothelial cell 5-HT receptors by use of tryptamine analogues

Br J Pharmacol. 1987 Jun;91(2):321-31. doi: 10.1111/j.1476-5381.1987.tb10287.x.

Abstract

In ring preparations of the rabbit external jugular vein contracted with the thromboxane-mimetic U-46619, submicromolar concentrations of 5-hydroxytryptamine (5-HT) and chemically related analogues produced relaxations that were dependent on the integrity of the vascular endothelium. The receptor mediating endothelium-dependent relaxations was evidently similar to previously described endothelial 5-HT receptors since relaxation responses to alpha-methyl-5-HT were not blocked by atropine, (+/-)-propranolol, yohimbine, indomethacin, ketanserin or MDL-72222, but were non-competitively antagonized by methysergide, methiothepin and cyproheptadine. The activities of some tryptamine agonists and antagonists at the endothelial 5-HT receptor in rabbit jugular vein were compared with their activities at the smooth muscle 5-HT2-receptor in rabbit aortic rings. Differences in the tryptamines' affinities and relative efficacies showed that the endothelial 5-HT receptor was not of the 5-HT2-type. The high agonist potencies of 5-HT and 5-carboxamidotryptamine, the susceptibility to antagonism by both methiothepin and methysergide and the resistance to blockade by selective 5-HT2 and 5-HT3 ('M') receptor antagonists implies that the endothelial receptor belongs to the '5-HT1-like' class. However, the agonist potency order 5-HT = alpha-methyl-5-HT greater than 5-carboxamidotryptamine suggested that the receptor is not the same as the peripheral '5-HT1-like' receptors reported to mediate directly contraction of the dog saphenous vein or relaxation of vascular and non-vascular smooth muscles. At these receptors, the potency order is 5-carboxamidotryptamine greater than 5-HT greater than alpha-methyl-5-HT. These results constitute preliminary evidence that peripheral '5-HT1-like' receptors, like central 5-HT1 recognition sites, are a heterogeneous population. Further comparative studies with a wider range of receptor probes are necessary to establish whether or not these receptors represent functional counterparts of the ligand binding sites in the brain.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Aorta, Thoracic / drug effects
  • Endothelium / drug effects*
  • In Vitro Techniques
  • Jugular Veins / drug effects
  • Male
  • Muscle, Smooth, Vascular / drug effects*
  • Rabbits
  • Receptors, Serotonin / drug effects*
  • Serotonin / analogs & derivatives
  • Serotonin / pharmacology
  • Serotonin / physiology
  • Serotonin Antagonists / pharmacology
  • Tryptamines / pharmacology*
  • Vasodilation / drug effects

Substances

  • Receptors, Serotonin
  • Serotonin Antagonists
  • Tryptamines
  • alpha-methylserotonin
  • Serotonin