PHARMACOLOGICAL CHARACTERIZATION OF THE HISTAMINE H-3 RECEPTOR IN THERAT HIPPOCAMPUS

The purpose of this report was to pharmacologically characterise the h istamine H-3 in the rat hippocampus using radioligand binding studies with the H-3 receptor antagonist [I-125]iodophenpropit and the H-3 rec eptor mediated inhibition of [H-3]noradrenaline release. A dissociatio n constant of 0.33 nM and a maximal number of binding sites of 125 fmo l/mg protein were found for [I-125]iodophenpropit. Competition studies showed stereoselectivity for the (R) and (S) enantiomers of alpha-met hylhistamine and 10 mu M of GTP(gamma) S shifted the curve of (R)-alph a-methylhistamine rightwards. Up to 1 mu M, (R)-alpha-methylhistamine displaced only 30% whereas the tested H-3-antagonists displaced 50-60% of the total [I-125]iodophenpropit bound. This indicates the presence of an additional non-H-3 receptor binding site(s) for [I-125]iodophen propit in the rat hippocampus. This secondary site shows low affinity for H-3 agonists, but high affinity for the tested H-3 antagonists. El ectrically evoked [H-3]acetylcholine release was shown in slices of ra t hippocampus. No H-3 receptor modulation of [H-3]acetylcholine releas e from hippocampal slices was detectable. However, H-3 receptor activa tion inhibited 42% of the electrically-evoked [H-3]noradrenaline relea se in rat hippocampal slices. The inhibition of [H-3]noradrenaline rel ease was effectively antagonized by the H-3 antagonists thioperamide a nd burimamide. We describe the pharmacological identification of the h istamine H-3 receptor in the rat hippocampus and its similarities and differences from the cortical H-3 receptor. These studies enable us to investigate changes in density and functionality of the hippocampal H -3 receptor under (patho)physiological conditions. (C) 1998 Elsevier S cience B.V.