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Actions of serotonin antagonists on cholera-toxin-induced intestinal fluid secretion

A Sjöqvist1, J Cassuto, M Jodal

  • 1Department of Physiology, University of Göteborg, Sweden.

Acta Physiologica Scandinavica
|July 1, 1992
PubMed

Insights

Several serotonin (5-hydroxytryptamine or 5-HT) receptor antagonists were tested in rats. Granisetron and ondansetron significantly reduced cholera toxin-induced intestinal fluid secretion, suggesting a role for 5-HT3 receptors.

Area of Science:

  • Pharmacology
  • Gastroenterology
  • Neuroscience

Background:

  • Cholera toxin induces intestinal fluid secretion via complex mechanisms.
  • Serotonin (5-hydroxytryptamine or 5-HT) is implicated in regulating intestinal function.
  • The specific 5-HT receptors involved in cholera toxin-induced secretion are not fully elucidated.

Purpose of the Study:

  • To investigate the effects of various 5-HT receptor antagonists on cholera toxin-induced intestinal fluid secretion in rats.
  • To identify potential 5-HT receptor subtypes involved in this secretory process.

Main Methods:

  • In vivo administration of five 5-HT receptor antagonists (2-bromo-LSD, granisetron, ketanserin, methysergide, ondansetron) in rats.
  • Assessment of intestinal fluid secretion evoked by cholera toxin.
  • Administration of 5-HT to evoke intestinal secretion and study receptor localization.
  • Use of zimeldine, a 5-HT reuptake inhibitor, to explore the role of 5-HT accumulation.

Main Results:

  • Granisetron and ondansetron significantly reduced cholera toxin-induced intestinal fluid secretion.
  • Ketanserin showed no effect, while methysergide demonstrated a diminishing effect, particularly with intravenous infusion.
  • Experiments suggested the involvement of 5-HT3 receptors, potentially 5-HT1 receptors, located in villus tissue.
  • Zimeldine diminished choleraic secretion, possibly due to 5-HT tachyphylaxis from synaptic cleft accumulation.

Conclusions:

  • The findings suggest that 5-HT3 receptors, and possibly 5-HT1 receptors, play a significant role in cholera toxin-induced intestinal fluid secretion.
  • These receptors are likely located within the intestinal villus tissue.
  • Modulation of 5-HT neurotransmission, including reuptake inhibition, can impact cholera toxin-induced secretion.

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