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. 1994 Oct;113(2):355–362. doi: 10.1111/j.1476-5381.1994.tb16995.x

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

F P Jansen 1, T S Wu 1, H P Voss 1, H W Steinbusch 1, R C Vollinga 1, B Rademaker 1, A Bast 1, H Timmerman 1
PMCID: PMC1510107  PMID: 7834183

Abstract

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.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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