The mouse 5-hydroxytryptamine 1B receptor is localized predominantly on axon terminals

Abstract

The 5-hydroxytryptamine 1B receptor is a serotonin receptor subtype which is expressed predominantly in the basal ganglia. It has been suggested to play a role in movement and appetite control as well as in certain pathological states such as migraine. The recent cloning of the 5-hydroxytryptamine 1B gene as well as the discovery of a radioligand that labels in rodents 5-hydroxytryptamine 1B and possibly 5-hydroxytryptamine 1Dα receptors (S-CM-G[ 125I]TNH 2) allowed us to compare the distribution of the messenger RNA and of the protein in mouse brain sections. A high 5-hydroxytryptamine 1B messenger RNA level is found in the caudate-putamen in medium spiny neurons that project to the globus pallidus and the substantia nigra. In contrast, no messenger RNA is expressed in the globus pallidus and substantia nigra although these structures reveal the highest level of 5-hydroxytryptamine 1B binding sites. In the hippocampus, 5-hydroxytryptamine 1B messenger RNA is localized in the cell bodies of pyramidal cells of the CA1 field while the protein is found predominantly in the dorsal subiculum, a projection zone for the CA1 pyramidal neurons. In the cerebellum, 5-hydroxytryptamine 1B messenger RNA is expressed in the Purkinje cells, which display no receptor binding sites. Conversely, moderate binding is found in the deep nuclei of the cerebellum, the main projection zone of the Purkinje cells. 5-Hydroxytryptamine 1B sites are also detected in the superficial gray layer of the superior colliculus and the lateral geniculate nucleus, brain regions containing the terminals of retinal ganglion cells. The soma of these ganglion cells express high levels of 5-hydroxytryptamine 1B messenger RNA while no 5-hydroxytryptamine 1B binding sites were found in the retina. This study demonstrates that the main brain regions, expressing 5-hydroxytrypamine 1B messenger RNA contain low densities of 5-hydroxytryptamine 1B binding sites. Conversely, the major projection areas of these anatomical structures do not express detectable levels of 5-hydroxytryptamine 1B messenger RNA, but present a high density of binding sites. In addition, our data suggest that the distribution of the 5-hydroxytryptamine 1Dα binding sites is different from that of the 5-hydroxytryptamine 1Dα messenger RNA. These results together with previous lesion studies, indicate that the 5-hydroxytryptamine 1B and possibly the 5-hydroxytryptamine 1Dα receptors are localized predominantly on axon terminals, while their expression is low or absent at the somatodendritic level. The 5-hydroxytryptamine 1B and 5-hydroxytryptamine 1Dα proteins might therefore contain an addressing signal allowing their transport toward nerve endings. This localization is in good agreement with the fact that the 5-hydroxytryptamine 1B receptors have been shown to inhibit neurotransmitter release from nerve terminals.