Evidence that histamine homologues discriminate between H-3-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-alph a-methylhistamine) to sites in guinea-pig cerebral cortex and ileum longitu dinal 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 long itudinal 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 o f [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 cerebr al cortex and ileum longitudinal muscle myenteric plexus expressing histami ne 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 discr iminate between the receptor populations in the two tissues. Thus, the esti mated affinity of five imidazole unbranched alkylamines (histamine, homohis tamine, VUF4701, VUF4732 and impentamine) were significantly higher in the guinea-pig cerebral cortex than in the ileum longitudinal muscle myenteric plexus assay.