5-Hydroxytryptamine affects rat migrating myoelectric complexes through different receptor subtypes: evidence from 5-hydroxytryptophan administration

Life Sci. 1990;46(17):1207-16. doi: 10.1016/0024-3205(90)90495-d.

Abstract

The effect of the serotonin precursor 5-hydroxytryptophan (5-HTP) on jejunal migrating myoelectric complexes (MMCs) was investigated in conscious rats. Subcutaneous administration of low doses of 5-HTP (1-2 mg/kg) shortened the period between migrating complexes, whereas high doses of the compound (4-8 mg/kg) disrupted the MMC pattern. The serotonin (5-HT2) antagonist methysergide (8 mg/kg s.c.) did not alter basal MMC, neither did it prevent the effect of a low dose of 5-HTP; conversely, it antagonized the disruption due to the high dose. The 5-HT3 antagonist ICS 205-930 (30 micrograms/kg s.c.) decreased MMC frequency; administration of 2 mg/kg 5-HTP following ICS 205-930 brought the frequency of myoelectric complexes back to basal values. Both effects of 5-HTP were prevented by the decarboxylase inhibitor benserazide (85 mg/kg i.p.), which per se caused a transient inhibition of spiking activity. The results suggest that rat MMCs can be influenced in a composite fashion by progressively increasing concentrations of 5-HT, which in turn activate different receptor subtypes. A peripheral neuronal receptor, probably belonging to the 5-HT3 subclass, mediates the increase in MMC frequency observed after low doses of 5-HTP; higher levels of serotonin activate 5-HT2 receptors, causing disruption of cycling activity. Additionally, 5-HT3 receptors, but not 5-HT2, appear to be relevant for the regulation of the MMC pattern by the endogenous amine.

MeSH terms

  • 5-Hydroxytryptophan*
  • Animals
  • Benserazide
  • Electroencephalography
  • Indoles
  • Jejunum / drug effects
  • Jejunum / innervation
  • Jejunum / physiology*
  • Male
  • Methysergide
  • Muscles / drug effects
  • Muscles / innervation
  • Muscles / physiology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Serotonin / physiology*
  • Serotonin / physiology*
  • Serotonin Antagonists
  • Tropisetron

Substances

  • Indoles
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin
  • Tropisetron
  • Benserazide
  • 5-Hydroxytryptophan
  • Methysergide