The profiles of human and primate [3H]Nalpha-methylhistamine binding differ from that of rodents

Characterization of the histamine H3 receptor in rodent species has been extensive but limited characterization has been done with primate or human tissue. We have characterized the binding of [3H]Nalpha-methylhistamine to cynomolgus monkey and human brain membranes to determine whether there are an...

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Bibliographic Details
Published in:European journal of pharmacology 1999-07, Vol.377 (2-3), p.233-239
Main Authors: West, Jr, R E, Wu, R L, Billah, M M, Egan, R W, Anthes, J C
Format: Article
Language:English
Subjects:
Animals
Brain - metabolism
Burimamide - metabolism
Cell Membrane - metabolism
Guanine Nucleotides - pharmacology
Humans
In Vitro Techniques
Macaca fascicularis
Methylhistamines - metabolism
Piperidines - metabolism
Receptors, Histamine - metabolism
Species Specificity
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Summary:Characterization of the histamine H3 receptor in rodent species has been extensive but limited characterization has been done with primate or human tissue. We have characterized the binding of [3H]Nalpha-methylhistamine to cynomolgus monkey and human brain membranes to determine whether there are any significant differences among species' pharmacology. In monkey, [3H]Nalpha-methylhistamine bound, in a guanine nucleotide-sensitive fashion, to an apparently homogeneous class of sites at equilibrium (K(D) = 1.4 nM, Bmax = 34 fmol/mg protein). The profile of binding was broadly similar to that of rodents, with a couple of significant differences. Most notably, the potency of the histamine H3-receptor-specific antagonist thioperamide (Ki = 240 nM) was substantially less than reported for rodents and under assay conditions that yield a two-site curve fit in rodents only a single class of thioperamide binding sites was detected in monkey. Burimamide, however, yielded a two-site curve fit (KiH = 6.7 nM, KiL = 1100 nM) independent of the presence of sodium in the assay, as it does in rodents. Characterization of the human brain histamine H3 receptor showed that it was similar to the monkey and not rodent receptor. Our findings indicate that differences between primate and rodent histamine H3 receptors of potentially serious importance for the discovery of antagonists active in humans do exist.
ISSN:0014-2999