Localization of 5-HT1B, 5-HT1Dα, 5-HT1E and 5-HT1F receptor messenger RNA in rodent and primate brain

Comparison of the localization of the mRNAs to the regional distributions of the 5-HT1B and 5- HT1D binding sites in rat brain revealed that both receptor subtypes could be putative presynaptic heteroreceptors, modulating the release of various neurotransmitters in the central nervous system.

Abstract

In situ hybridization histochemistry (ISHH) was used to study the distribution of various 5-HT1 receptor messenger RNAs (mRNA) in the mammalian nervous system. Since the cDNAs encoding the different 5-HT1 receptors, have not been cloned in one single species, brains of the species appropriate for the 5-HT1 receptor messenger RNA (mRNA) have been used. Thus, 5-HT1B and 5-HT1D alpha mRNA were determined in rat and mouse brain, while 5-HT1E and 5-HT1F mRNA were studied in human (and monkey) and guinea-pig brain, respectively. 5-HT1B and 5-HT1D alpha hybridization signals were predominantly present in caudate-putamen and cortical areas; in addition, 5-HT1B mRNA was also detected in hippocampus, cerebellum and cerebral arteries. In general, the distribution of 5-HT1B mRNA was characterized by high densities, whereas 5-HT1D alpha mRNA was expressed at very low levels. Comparison of the localization of the mRNAs to the regional distributions of the 5-HT1B and 5-HT1D binding sites in rat brain (described in a previous study), revealed that both receptor subtypes could be putative presynaptic heteroreceptors, modulating the release of various neurotransmitters in the central nervous system. The mRNA encoding the recently cloned 5-HT1E receptor, which has low affinity for the 5-HT1 receptor ligand 5-carboxamidotryptamine (5-CT), was localized in human brain. It was found to be present in cortical areas, caudate, putamen and amygdala, areas known to contain 5-CT insensitive 5-HT1 binding sites. The regional distribution of the 5-HT1F mRNA was determined in guinea-pig brain: high densities were observed in various cortical areas, the hippocampal formation and claustrum, which are regions known to contain 5-CT insensitive 5-HT1 or non 5-HT1A/1B/IC/ID [3H]5-HT binding sites. Altogether, this ISHH study describes the distribution of mRNAs of recently cloned 5-HT1 receptors in rodent and primate brain and compares these results to the distribution of the heterogeneous population of 5-HT1 binding sites.