Distribution of the histamine H2 receptor in monkey brain and its mRNA localization in monkey and human brain

Abstract

The distribution of histamine H2 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. [125I]Iodoaminopotentidine ([125I]‐APT), a reversible, high specific activity antagonist with high affinity and selectivity for the H2 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 H2 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 H2 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 H2 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 H2 receptors found in the striatum are synthesized by intrinsic cells and not by nigral dopaminergic cells. These striatal H2 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 H2 receptors detected by in situ hybridization, define the sites of synthesis of H2 receptors and are the basis for future, more detailed studies that should result in a better understanding of H2 receptor function. Synapse 38:343–354, 2000. © 2000 Wiley‐Liss, Inc.

Neuropharmacology of Histamine in Brain

“…The caudate putamen, ventral striatal complex, and amygdaloid nuclei (bed nucleus of the stria terminalis) are among the richest brain areas. The distribution of the mRNAs is generally in agreement with that of the corresponding binding sites [192,251,252]. In the striatum, the absence of mRNAs in the substantia nigra and the loss of binding sites in Huntington's disease [253] indicate that H 2 receptors are expressed by intrinsic neurons.…”

“…Autoradiographic localization of the H 2 receptor using [ 125 I]iodoaminopotentidine in the guinea pig [211,251], monkey, and human brain [191,210,252] shows it distributed heterogeneously ( Fig. 9.2).…”

Selective Modulation of Histaminergic Inputs on Projection Neurons of Cerebellum Rapidly Promotes Motor Coordination via HCN Channels

“…Autoradiographic mapping, immunohistochemical analysis and in situ hybridization data have also indicated the presence of histamine receptors in the cerebellum [10][11][12][13]. Interestingly, by using extracellular recordings on rat brain slices, we find that histamine excites cerebellar Purkinje cells, granule cells, and nuclear neurons [1,14], and improves motor performances mediated by the cerebellar interpositus nucleus (IN) or fastigial nucleus (FN) [14,15].…”

“…7b). A two-way ANOVA with repeated measures revealed a significant effect of time (F (3,135) =20.330, P<0.01), treatment (F (4,45) =6.668, P<0.01), and time×treatment interaction (F (12,135) =50.949, P<0.01). Newman-Keuls post hoc test indicated that microinjection of histamine (n=10) into the cerebellar IN significantly lengthened the endurance time of rats on the rotating rod 0 h (P<0.01, Fig.…”

Excitatory effect of histamine on neuronal activity of rat cerebellar fastigial nucleus in vitro

“…Immunohistochemical studies have offered convincing evidence that the histaminecontaining neurons project from the tuberomammillary nucleus to both cortex and nuclei of the cerebellum [4,5] . Autoradiographic mapping, immunohistochemical analysis and in situ hybridization experiments have indicated the presence of histamine H 1 , H 2 and H 3 receptors in rat cerebellar cortex and deep cerebellar nuclei [6][7][8][9][10][11][12] . All of these studies reveal the existence of the direct histaminergic pathway between hypothalamus and cerebellum [13] .…”