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

Characterization of the histamine H-3 receptor in rodent species has been e xtensive but limited characterization has been done with primate or human t issue. We have characterized the binding of [H-3]N-alpha-methylhistamine to cynomolgus monkey and human brain membranes to determine whether there are any significant differences among species' pharmacology. In monkey, [H-3]N -alpha-methylhistamine bound, in a guanine nucleotide-sensitive fashion, to an apparently homogeneous class of sites at equilibrium (K-D = 1.4 nM, B-m ax = 34 fmol/mg protein). The profile of binding was broadly similar to tha t of rodents, with a couple of significant differences. Most notably, the p otency of the histamine H-3-receptor-specific antagonist thioperamide (K-i = 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 o f thioperamide binding sites was detected in monkey. Burimamide, however, y ielded a two-site curve fit (K-iH = 6.7 nM, K-iL = 1100 nM) independent of the presence of sodium in the assay, as it does in rodents. Characterizatio n of the human brain histamine H-3 receptor showed that it was similar to t he monkey and not rodent receptor. Our findings indicate that differences b etween primate and rodent histamine H-3 receptors of potentially serious im portance for the discovery of antagonists active in humans do exist. (C) 19 99 Elsevier Science B.V. All rights reserved.