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

Abstract

1The binding of the first selective radiolabelled histamine H3-receptor 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 (GTPTyS; 100 pLM) 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 GTPyS. 7 Histamine competition binding curves were shifted to the right by different nucleotides (100 tiM) with a rank order of potency GTPyS>Gpp(NH)p, GTP. 8 In vitro autoradiographic studies revealed a heterogeneous distribution of ['251]-iodophenpropit binding 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, ['251I]-iodophenpropit, meets the criteria for a suitable radioligand for histamine H3-receptor binding studies in rat brain.

Pharmacological properties of cardiovascular histamine H1 receptor binding sites: characterisation with 2-phenylhistamines

“…The guanine nucleotide-sensitive, biphasic displacement could be interpreted as the result of the known agonist-induced formation of a ternary complex between the agonist-receptor complex and G-proteins as proposed by Jansen et al (1994), (for review see also Kenakin 1993), thus confirming the agonistic nature of the above drugs, already shown in the functional studies (Zingel et al 1995;Leschke et al 1995).…”

Histamine H3-receptor isoforms

“…There has been speculation of H 3 receptor heterogeneity and subtypes based on radioligand binding [32][33][34][35] or functional assays [36][37][38][39] using native H 3 receptors. Although the existence of isoforms derived from the same gene with limited pharmacological differences may account partly for these observations, and the lack of (R)-[a-3 H]-methylhistamine binding in H 3 knock-out mice (mH 3 -/-) [30] corroborates that a single gene may give rise to the reported H 3 receptor heterogeneity, as yet the H 3 -receptor heterogeneity has not been attributed to the presence of particular H 3 -receptor isoforms.…”

Evidence that histamine homologues discriminate between H3‐receptors in guinea‐pig cerebral cortex and ileum longitudinal muscle myenteric plexus

“…Radioligand binding studies have been used extensively (e.g. Arrang et al ., 1990; Jansen et al ., 1994; Clark & Hill, 1995), together with functional bioassay studies (e.g. Arrang et al ., 1985; Clapham & Kilpatrick, 1992; Schlicker et al ., 1996), to characterize histamine H 3 ‐receptors in central nervous system tissue.…”