Binding of [3H]p-aminoclonidine to two sites, alpha 2-adrenoceptors and imidazoline binding sites: distribution of imidazoline binding sites in rat brain

Binding sites labeled by 3H]p-aminoclonidine ( 3H]PAC) were investigated by the competitive analysis with imidazoline and non-imidazoline derivatives. Phenylethylamine derivatives displaced only the part of specific sites for 3H]PAC, which was considered as alpha 2-adrenoceptor, whereas imidazoline derivatives, such as clonidine and tolazoline, competed for a further specific binding of 3H]PAC to the non-adrenergic sites, in addition to the alpha 2-adrenoceptor. Because the non-adrenergic sites were specific for the imidazoline structure, they were termed imidazoline sites. The imidazoline sites were not distributed uniformly among rat brain regions. In striatum, hippocampus and medulla oblongata, they occupied 39.6, 33.0 and 36.5% of the specific binding of 3H]PAC, respectively. Saturation isotherms revealed that Kd and Bmax of imidazoline sites for 3H]PAC were 3.09 +/- 0.59 nM, 27.4 +/- 1.7 fmol/mg protein and 2.23 +/- 0.29 nM, 21.0 +/- 1.5 fmol/mg protein in striatum and hippocampus, respectively. Because imidazoline binding sites also displayed weak affinities for imidazole compounds, such as histamine and cimetidine, the imidazoline site may be a subtype of histamine H2-receptor.