Distribution of the histamine H(2) receptor in monkey brain and its mRNA localization in monkey and human brain.

Abstract

The distribution of histamine H(2) receptor mRNA was determined by in situ hybridization histochemistry in human and monkey brain. In the case of monkey brain, we combined this technique with receptor ligand autoradiography to compare the distribution of mRNA and receptor binding sites. [(125)I]Iodoaminopotentidine ([(125)I]-APT), a reversible, high specific activity antagonist with high affinity and selectivity for the H(2) receptor, was used for receptor autoradiography. Radiolabeled oligonucleotides derived from the human mRNA sequence encoding this receptor were used as hybridization probes. The highest density of the H(2) receptor mRNA in human and monkey brain was found in caudate and putamen nuclei and external layers of cerebral cortex. Moderate levels were seen in the hippocampal formation and lower densities in the dentate nucleus of cerebellum. Areas such as globus pallidus, amygdaloid complex, cerebellar cortex, and substantia nigra were devoid of hybridization signal. The distribution of H(2) receptor mRNA in monkey brain is generally in good agreement with that of the corresponding binding sites: prominent in caudate, putamen, accumbens nuclei, and cortical areas. The hippocampus showed lower densities of receptors and low levels were detected in the globus pallidus pars lateralis. No binding sites were seen in amygdaloid complex and substantia nigra. The distribution of histaminergic innervation is in good correlation with the areas of high density for H(2) receptors: caudate, putamen, and external layers of cerebral cortex in monkey and human brain. The presence of mRNA in caudate and putamen nuclei, together with its absence from substantia nigra, suggests that the H(2) receptors found in the striatum are synthesized by intrinsic cells and not by nigral dopaminergic cells. These striatal H(2) receptors may be located on short circuit striatal interneurons or somatodendritically on striatal projection neurons which project to the globus pallidus pars lateralis. In conclusion, the present results, which constitute, to our knowledge, the first report of the regional distribution of mRNA encoding H(2) receptors detected by in situ hybridization, define the sites of synthesis of H(2) receptors and are the basis for future, more detailed studies that should result in a better understanding of H(2) receptor function.