Characterization of histamine H-3 receptors in mouse brain using the H-3 antagonist [I-125]iodophenpropit

We have characterized the binding of the histamine H-3 receptor antagonist [I-125]iodophenpropit to mouse brain. [I-125]Iodophenpropit saturably bound to mouse brain membranes with a pK(d)-value of 9.31+/-0.04 nM and a recept or binding density of 290+/-8 fmol per mg protein. Saturation binding analy sis revealed binding of [I-125]iodophenpropit to a single class of sites, s howing linear Scatchard plots and Hill coefficients not different from unit y (n(H)=0.98+/-0.02). At a concentration of 0.25 nM [I-125]iodophenpropit, specific binding represented about 75% of the total binding. Competition bi nding curves for H-3 receptor antagonists were fitted beat to a one-site mo del, showing pK(i)-values in general accordance with the pA(2)-values obtai ned in mouse cerebral cortex. Displacement of [I-125]iodophenpropit by the H-3 receptor agonists (R)-alpha-methylhistamine, immepip, imetit and histam ine were fitted best to a two-site model. Competition binding curves of (R) -alpha-methylhistamine showed a rightward shift upon incubation with GTP ga mma S (10 mu M), indicating the involvement of G-proteins in H-3 agonist bi nding. In contrast, competition binding curves of the antagonists iodophenp ropit, thioperamide and burimamide were not affected by GTP gamma S (10 mu M). Autoradiographic experiments showed that [I-125]iodophenpropit binding sites were heterogeneously distributed, similarly to the distribution of hi stamine H-3 receptors reported in rat brain. Highest densities were observe d in the cerebral cortex, the striatum, the nucleus accumbens, the globus p allidus and the substantia nigra. In conclusion, we have demonstrated that in mouse brain, [I-125]iodophenpro pit selectively binds to histamine H-3 receptors. We also observed that the mouse brain H-3 receptors labelled by[I-125]iodophenpropit displayed bindi ng characteristics and a distribution similar to rat brain.