Detailed distribution of Neurokinin 3 receptors in the rat, guinea pig and gerbil brain: a comparative autoradiographic study.
The neurokinin 3 (NK3) receptor is predominantly expressed in the central nervous system (CNS). Species differences in neurokinin 3 (NK3) receptor pharmacology have led to the preferential use of guinea pigs and gerbils in the characterization of non-peptide NK3 antagonists. Little is known about the central localization of NK3 receptors in the CNS of these species. To study this, [(3)H]senktide and [(3)H]SR 142801 were used in autoradiography experiments to visualize the NK3 receptors in the guinea pig and gerbil brain and compared to with the distribution of [(3)H]senktide binding sites in the rat brain. In the three species, the NK3 receptor was similarly distributed within the cerebral cortex, the zona incerta, the medial habenula, the amygdaloid complex, the superior colliculus and the interpeduncular nucleus. Outside of these structures, our study has revealed that each species displayed a specific distribution pattern of central NK3 receptors. The rat was the only species where NK3 receptors could be visualized in the striatum, the supraoptic nucleus and the paraventricular nucleus of the hypothalamus. The guinea pig differed mainly from the two other species by the absence of detectable binding sites in the substantia nigra pars compacta and the ventral tegmental area. A specific localization of NK3 receptors in the anterodorsal and anteroventral thalamic nuclei characterized the gerbil. This last species is also unique by in the higher level of NK3 receptors in the dorsal and median raphe nuclei. All these differences suggest that the NK3 receptor mediates different functions in different species.
Langlois
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X
Department of Biochemical Pharmacology, Janssen Research Foundation, B-2340 Beerse, Belgium. xlangloi@janbe.jnj.com
Wintmolders
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C
te Riele
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P
Leysen
J E
JE
Jurzak
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M
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D005849:Gerbillinae; D006168:Guinea Pigs; D008297:Male; D008566:Membranes; D010446:Peptide Fragments / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018042:Receptors, Neurokinin-3 / Q000378:metabolism*; D013045:Species Specificity; D013373:Substance P / Q000031:analogs & derivatives* / Q000378:metabolism
D010446:Peptide Fragments; D010880:Piperidines; D018042:Receptors, Neurokinin-3; C054724:senktide; D013373:Substance P; C091554:SR 142801