Characterization of the receptors involved in the 5-HT-induced excitation of canine antral longitudinal muscle

Br J Pharmacol. 2001 Nov;134(6):1351-9. doi: 10.1038/sj.bjp.0704376.

Abstract

1. We aimed to characterize the 5-HT receptors involved in the 5-HT-induced effect on electrically induced contractions of dog antrum longitudinal muscle in vitro. 2. In the presence of L-NOARG (0.1 mM), electrical field stimulation (EFS) induced atropine- and tetrodotoxin-sensitive contractions. Tetrodotoxin or atropine left any agonist tested ineffective. These EFS-induced contractions were on average enhanced by 5-HT (0.3 microM), however, pronounced variation in the response to 5-HT was observed. There were non-significant trends of the selective 5-HT3 receptor antagonist granisetron (1 microM), and methysergide (1 microM; preventing interactions of 5-HT with 5-HT1, 5-HT2, 5-ht5, 5-HT6 and 5-HT7 receptors) to increase the response to 5-HT. The selective 5-HT4 receptor antagonist GR 113808 (0.1 microM) displayed a non-significant trend to inhibit the 5-HT-induced increase. 3. Combination experiments with methysergide (1 microM), granisetron (1 microM) and GR 113808 (0.1 microM) revealed that the 5-HT (0.3 microM)-induced response consisted of (1) an excitatory component blocked by GR 113808, (2) excitatory and inhibitory components both blocked by methysergide. 4. The selective 5-HT4 receptor agonist prucalopride (0.3 microM) increased EFS-induced contractions, an effect prevented by GR 113808 (0.1 microM). 5. The increase of EFS-induced contractions by the preferential 5-HT2 receptor agonist alpha-Me-5-HT (0.3 microM) was antagonized by 5-HT2B receptor antagonists. 6. The 5-HT1/5-HT7 receptor agonist 5-carboxamidotryptamine (5-CT; 0.3 microM) inhibited EFS-induced contractions. This was prevented by methysergide (1 microM), the 5-HT7 receptor antagonist mesulergine (0.3 microM) and the selective 5-HT7 receptor antagonist SB-269970 (0.3 microM). 7. In the presence of GR 113808 (0.1 microM), alpha-Me-5-HT (1 microM) increased EFS-induced contractions. The 5-HT (0.3 microM)-induced inhibition of the stimulation by alpha-Me-5-HT was prevented by SB-269970 (0.3 microM). 8. In conclusion, dog antral longitudinal muscle is endowed with (1) excitatory neuronal 5-HT4 receptors and 5-HT2B receptors and (2) inhibitory smooth muscle 5-HT7 receptors.

MeSH terms

  • Animals
  • Atropine / pharmacology
  • Dogs
  • Electric Stimulation
  • Female
  • Gastrointestinal Motility / drug effects*
  • Gastrointestinal Motility / physiology
  • Granisetron / pharmacology
  • In Vitro Techniques
  • Indoles / pharmacology
  • Male
  • Methysergide / pharmacology
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / physiology
  • Nitroarginine / pharmacology*
  • Pyloric Antrum / drug effects
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology*
  • Serotonin / pharmacology*
  • Serotonin Antagonists / pharmacology*
  • Sulfonamides / pharmacology
  • Tetrodotoxin / pharmacology
  • Tryptamines / pharmacology

Substances

  • Indoles
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Sulfonamides
  • Tryptamines
  • Nitroarginine
  • Serotonin
  • Tetrodotoxin
  • Atropine
  • Granisetron
  • Methysergide
  • GR 113808