Characterization of the binding of the first selective radiolabelled histamine H3-receptor antagonist, [125I]-iodophenpropit, to rat brain

Br J Pharmacol. 1994 Oct;113(2):355-62. doi: 10.1111/j.1476-5381.1994.tb16995.x.


1. The binding of the first selective radiolabelled histamine H3-receptor antagonist [125I]-iodophenpropit to rat cerebral cortex membranes was characterized. 2. [125I]-iodophenpropit, radiolabelled to a high specific activity of 1900 Ci mmol-1, saturably bound to a single class of sites with a KD of 0.57 +/- 0.16 nM (n = 4) and Bmax of 268 +/- 119 fmol mg-1 protein. 3. Specific binding at a concentration below 1 nM represented 50 to 60% of total binding. 4. Binding of [125I]-iodophenpropit to rat cerebral cortex membranes was readily displaced by histamine H3-agonists and antagonists. In contrast, the inhibitory potencies of selective histamine H1- and H2-receptor ligands were very low. 5. [125I]-iodophenpropit was biphasically displaced by the histamine H3-receptor antagonists, burimamide and dimaprit, which may indicate the existence of histamine H3-receptor subtypes. Other histamine H3-receptor antagonists showed a monophasic displacement. 6. Competition binding curves of H3-agonists were biphasic and showed a rightward shift upon the addition of the nonhydrolysable GTP analogue, guanosine 5'-o-(3-thio) triphosphate (GTP gamma S; 100 microM) which implicates the interaction of histamine H3-receptors with G-proteins. The affinities of the H3-receptor antagonists iodophenpropit, thioperamide and burimamide were not altered by GTP gamma S. 7. Histamine competition binding curves were shifted to the right by different nucleotides (100 microM) with a rank order of potency GTP gamma S > Gpp(NH)p, GTP. 8 In vitro autoradiographic studies revealed a heterogeneous distribution of [125I]-iodophenpropitbinding sites in rat brain, with highest densities observed in specific cerebral cortical areas and layers,the caudate-putamen complex, the olfactory tubercles, the hippocampal formation, the amygdala complex, the hypothalamic area and the mammillary bodies.9 It is concluded that the histamine H3-receptor antagonist, [125I]-iodophenpropit, meets the criteria fo ra suitable radioligand for histamine H3-receptor binding studies in rat brain.

MeSH terms

  • Animals
  • Autoradiography
  • Binding, Competitive / drug effects
  • Brain / metabolism*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Guanine Nucleotides / pharmacology
  • Histamine Agonists / pharmacology
  • Histamine Antagonists / pharmacokinetics*
  • Imidazoles / pharmacokinetics*
  • In Vitro Techniques
  • Iodine Radioisotopes
  • Isothiuronium / analogs & derivatives*
  • Isothiuronium / pharmacokinetics
  • Male
  • Membranes / drug effects
  • Membranes / metabolism
  • Nerve Tissue Proteins / metabolism
  • Radioligand Assay
  • Rats
  • Rats, Wistar
  • Receptors, Histamine H3 / metabolism


  • Guanine Nucleotides
  • Histamine Agonists
  • Histamine Antagonists
  • Imidazoles
  • Iodine Radioisotopes
  • Nerve Tissue Proteins
  • Receptors, Histamine H3
  • Isothiuronium
  • iodophenpropit