Evidence that histamine homologues discriminate between H3-receptors in guinea-pig cerebral cortex and ileum longitudinal muscle myenteric plexus

1 The binding of the selective histamine H-3-receptor agonist ([H-3]-R-alpha-methylhistamine) to sites in guinea-pig cerebral cortex and ileum longitudinal muscle myenteric plexus has been characterized and a comparison made of the apparent affinities of a series of H-3-receptor ligands. 2 Saturation analysis suggested that [H-3]-R-alpha-methylhistamine labelled a homogeneous population of histamine H-3-receptors in guinea-pig cerebral cortex (pK(D) = 9.91 +/- 0.07; n(H) = 1.07 +/- 0.03; n = 5) and ileum longitudinal muscle myenteric plexus (pK(D) = 9.75 +/- 0.21; n(H) = 0.97 +/- 0.02; n = 5). There was no significant difference in the estimated affinity of [H-3]-R-alpha-methylhistamine in the two tissues. The cerebral cortex had a significantly higher receptor density (3.91 +/- 0.37 fmol mg(-1) tissue) than the ileum longitudinal muscle myenteric plexus (0.39 +/- 0.11 fmol mg(-1)). 3 Overall, the apparent affinities of compounds, classified as H-3-receptor ligands, in cerebral cortex and ileum longitudinal muscle myenteric plexus were well correlated (r = 0.91, P < 0.0001) and consistent with the cerebral cortex and ileum longitudinal muscle myenteric plexus expressing histamine H-3-receptor population(s) that are pharmacologically indistinguishable by the majority of histamine H-3-receptor ligands. However, it was evident that the homologues of histamine within this group of compounds could discriminate between the receptor populations in the two tissues. Thus, the estimated affinity of five imidazole unbranched alkylamines (histamine, homohistamine, VUF4701, VUF4732 and impentamine) were significantly higher in the guinea-pig cerebral cortex than in the ileum longitudinal muscle myenteric plexus assay.