Cloning and pharmacological characterization of the monkey histamine H3 receptor

Genetic and pharmacological aspects of histamine H3 receptor heterogeneity

“…These potency differences are not an artifact of receptor expression level of cloned vs. native receptors (Table 3), as shown in the comparison (West et al, 1999), our own studies (Fig. 4, Yao et al, 2003b;Curtis et al, 2003;Krueger et al, 2002), or in comparison of the cloned and native rat receptors, where tested compounds were of comparable affinity (Lovenberg et al, 2000b). Functional studies of [ 3 H]-histamine release in human and rat cortical slices also showed thioperamide to be 4-fold more potent in the rat .…”

“…The intercepts are highly statistically significantly different (P = 0.003). Potency data on these compounds have been reported (Yao et al, 2003b;Curtis et al, 2003;Krueger et al, 2002). have been observed at human isoforms 1 (hH 3 (445)) and the 80 amino acid shorter isoform 2 (hH 3 (365), Wellendorph et al, 2002). However other studies (Table 3) reported no affinity differences for ciproxifan, thioperamide or clobenpropit at these 2 human isoforms (Guenin et al, 2001), although clobenpropit failed to differentiate between high and low affinity sites in native receptors (Clark and Hill, 1995), so its lack of selectivity for splice isoforms is perhaps not surprising.…”

“…However, no agonist or antagonist compound demonstrated profound differential potency between hH 3 (365) and hH 3 (445). Potency data on these compounds have been reported (Yao et al, 2003b;Curtis et al, 2003;Krueger et al, 2002). Methods for the GTPgS binding assay have recently been published .…”

“…Moreover, the coupling of the H 3 receptor to the chimeric G-protein has also been successfully employed to evaluate the pharmacological characteristics of rat and monkey H 3 receptors and to compare them to the human receptor (Fig. 4, and Yao et al, 2003b) or with chimeric and mutant rat and human H 3 receptors, themselves (Yao et al, 2003a), revealing similar pharmacological profiles as seen in the binding assays described above.…”

Search for Histamine H3 Receptor Ligands with Combined Inhibitory Potency at HistamineN‐Methyltransferase: ω‐Piperidinoalkanamine Derivatives

“…Although G protein-coupled histamine H 3 receptors were described two decades ago by an elegant set of pharmacological experiments [3], their cloning and molecular characterization was not achieved until recently [4]. Today, valuable H 3 receptor information is available from various species, such as rat [5], mouse [6], guinea-pig [7], monkey [8], and human [4]. Major progress was also achieved to understand expression patterns, receptor subtypes, species-related pharmacological diversity [9], and constitutive activity [10].…”