HIGH-AFFINITY HISTAMINE BINDING-SITE IS THE H3 RECEPTOR - CHARACTERIZATION AND AUTORADIOGRAPHIC LOCALIZATION IN RAT-BRAIN

The binding of the histamine autoreceptor (H-3) agonist [H-3]-N-alpha-methylhistamine ([H-3]-N-MeHA) was examined in 25-mu-m thick rat forebrain sections. The specific binding was saturable and of high affinity: Scatchard analysis indicated a K(d) of 2 nM and a B(max) of 25 +/- 3 fmol/section. Under similar conditions, [H-3]-histamine ([H-3]-HA) bound with a K(d) of 8 nM and a B(max) of 20 +/- 2 fmol/section. Competition studies indicated that both ligands bound an identical site which had the pharmacological characteristics of the H-3 binding site. The high affinity binding of [H-3-N-MeHA was sensitive to the presence of 5'-guanylyl-imidodiphosphate, indicating that the binding site is likely coupled to a G-protein. Autoradiographic studies indicated the [H-3]-N-MeHA binding to be greatest in the nucleus accumbens, striatum, substantia nigra pars reticulata, and certain cortical areas. Striatal quinolinic acid lesions greatly reduced binding in both the striatum and ipsilateral substantia nigra, while 6-hydroxydopamine lesions of the nigrostriatal dopamine system were without effect on binding. Therefore, most of the H-3 binding sites in the basal ganglia are on striatonigral projection neurons. Cortical quinolinic acid lesions greatly reduced H-3 binding in cortex, indicating that the binding in cortex, as in striatum, is largely on intrinsic neurons, rather than on afferents such as histamine nerve terminals.