Characterization of brain neurotensin receptors using a new tool : levocabastine
(1989)
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- Levocabastine, a non-peptide antihistamine compound, inhibits, with high affinity and selectivity, neurotensin binding to the low affinity neurotensin sites (NTL-sites) in rat, mouse and hamster brain but not in various other mammalian species including man. <BR> The use of levocabastine enable to study separately the binding of radiolabelled neurotensin to the high affinity neurotensin binding sites (NTH-sites) and to the NTL-sites. NTH-sites are densely present in the substantia nigra, ventral tegmental area, cingulated cortex, entorhinal cortex, olfactory bulb, rhinal sulcus, superior colliculis and ventral dentate gyrus. They display the properties of a neurotransmitter receptor binding site and should be considered as the physiologically relevant neurotensin receptor. <BR> NTH-sites are situated on dopaminergic nerve ending both in the nigrostriatal and mesolimbic pathways. <BR> NTH- and NTL-sites are not high and low affinity states of a same receptor, since both neurotensin binding sites show different subcellular distribution patterns after isopycnic centrifugation in sucrose density gradients. <BR> Although they show strict stereospecific properties, NTL-sites have, as yet, no defined functional role and are likely to be considered as chemical recognition sites for neurotensin and for levocabastine. <BR> NTL-sites are homogeneously present in the various brain areas of the rat brain. They are distinct entities and have no relationship with the histamine-H1 receptors. NTL-sites are suggested to be localized on glial cells. <BR> During the ontogenic development, NTJ-sites peak in most brain areas between the 5th and the 10th day of postnatal life. They are then predominant in the cortical areas, but subsequently dramatically regress in many brain areas. In the substantia nigra NTH-sites peak at 15 days and slightly decrease in adulthood. NTL-sited start to appear only from the 15th day of life. <BR> Evidence is given herewith that only the NTH-sites can be involved with the regulation of the dopamine release in the rat brain. This knowledge is of essential importance for the development of neurotensin antagonists with potential therapeutic potency is psychiatry, which should therefore be compounds directed exclusively towards the high affinity neurotensin binding sites
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Schotte, A. (1989). Characterization of brain neurotensin receptors using a new tool : levocabastine. https://hdl.handle.net/2078.5/111591