Characterization of histamine H3 receptors inhibiting 5-HT release from porcine enterochromaffin cells: further evidence for H3 receptor heterogeneity

Naunyn Schmiedebergs Arch Pharmacol. 1994 Oct;350(4):375-9. doi: 10.1007/BF00178954.


The nature of the histamine receptor mediating inhibition of 5-HT release was investigated in strips of the porcine small intestine by investigating the effects of histamine ligands on the overflow of endogenous 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA). The overflow was measured by HPLC, combined with electrochemical detection and represents calcium-sensitive 5-HT release from enterochromaffin cells, as reported previously. The histamine H3 receptor selective agonists (R)-alpha-methyl-histamine and imetit inhibited the overflow of 5-HT maximally by 50-60%, with EC50 values of 48 and 3.2 nmol/l, respectively. Effects on 5-HT overflow were always accompanied by similar effects on the overflow of 5-HIAA. Thioperamide (100 nmol/l) shifted the concentration response curve of (R)-alpha-methyl-histamine to the right (pKB value 8.38). The inhibitory effect of 1 mumol/l (R)-alpha-methyl-histamine was antagonized in a concentration-dependent manner by thioperamide (IC50: 65 nmol/l) and dimaprit (IC50: 8.6 mumol/l); however, the effect of (R)-alpha-methyl-histamine was weakly antagonized by burimamide (by 38% at 100 mumol/l) and not significantly affected by other H3 receptor antagonists, such as impromidine, betahistine and phenyl-butanoyl-histamine (each up to 100 mumol/l). In conclusion, H3 receptors mediating inhibition of 5-HT release from porcine enterochromaffin cells have a particular pharmacological profile indicating that heterogeneity of H3 receptors may exist. The data suggest that histamine H3 receptors modulating 5-HT release in pig small intestine do not belong to either H3A or H3B receptors as defined in rat tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid
  • Drug Interactions
  • Enterochromaffin Cells / drug effects*
  • Enterochromaffin Cells / metabolism
  • Female
  • Histamine Agonists / metabolism
  • Histamine Agonists / pharmacology
  • Histamine Antagonists / pharmacology
  • Hydroxyindoleacetic Acid / metabolism
  • Intestine, Small / drug effects
  • Intestine, Small / metabolism
  • Male
  • Receptors, Histamine H3 / drug effects
  • Receptors, Histamine H3 / metabolism*
  • Serotonin / metabolism*
  • Swine


  • Histamine Agonists
  • Histamine Antagonists
  • Receptors, Histamine H3
  • Serotonin
  • Hydroxyindoleacetic Acid