Disease relevance of Nts

• NT receptor (R) mRNA was observed in more than 25% of the small dorsal root ganglion (DRG) neurons, which lacked neuropeptide Y NPY-R mRNA and essentially other neuropeptide mRNAs [1].
• As previously reported, NT (30 micrograms, ic) completely prevented the development of gastric ulcers in rats exposed to three hours of CRS [2].
• The results reinforce the hypothesis that hyperphagia in obesity is associated with a biochemical modification in the central nervous system because the peripheral status of NT and NPY was not modified in the obese rats [3].
• TRH, somatostatin and naloxone had no effect on neurotensin-induced hypothermia [4].
• Neurotensin had no effect on PGE2-induced hyperthermia [4].

Psychiatry related information on Nts

• The elevation in extracellular dopamine produced by DAMGO, but not by neurotensin, was positively correlated with the increase in motor activity [5].
• Mediation by neurotensin-receptors of effects of neurotensin on self-stimulation of the medial prefrontal cortex [6].
• Ventral tegmental area infusion of substance P, neurotensin and enkephalin: differential effects on feeding behavior [7].
• We recently demonstrated that microinjection of neurotensin into the ventral tegmental area produces behavioral hyperactivity similar to amphetamine-induced increase in exploratory behaviors, but lacking stereotypies [8].
• Neurotensin attenuates the reduction in alcohol drinking produced by angiotensin II [9].

High impact information on Nts

• Dopamine-containing cells of the substantia nigra, prominently implicated in the motor side effects of neuroleptics, possess dense concentrations of receptors for the putative peptide neurotransmitter, neurotensin [10].
• Neurotensin in the rat anterior pituitary gland [11].
• Neurotensin receptors are located on dopamine-containing neurones in rat midbrain [12].
• Bilateral injections of either neurotensin (NT; 0.3, 1 or 5 micrograms in 1 microliter artificial CSF) or haloperidol (HA; 2.5 or 5 micrograms in 1 microliter 0.3% tartaric acid) into nucleus accumbens of rats markedly diminished the forward locomotion and rearing induced by d-amphetamine (AM; 2 mg per kg, IP) [13].
• Excised introns for neurotensin RNA appear free to diffuse [14].

Chemical compound and disease context of Nts

• The expression of the gene encoding the neuroendocrine peptides neurotensin (NT) and neuromedin N is strictly dependent on simultaneous exposure to multiple inducers in PC12 pheochromocytoma cells [15].
• This study provides evidence suggesting that, in chronic gastric fistula rats, intracerebroventricularly administered NT (15-60 micrograms) significantly reduces both basal and pentagastrin-, 2-deoxy-D-glucose-, and carbachol-but not histamine-stimulated gastric acid secretion [16].
• The effects of neurotensin on the incidence and histology of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine were investigated in Wistar rats [17].
• Neurotensin and substance P given iv 5, 10, 20 and 30 minutes prior to blood collection produce hypoinsulinemia, hyperglucagonemia and hyperglycemia in the rat [18].
• 5. It is concluded that neurotensin excites ventral tegmental area neurones by activating a pertussis toxin-insensitive guanosine nucleotide-binding protein [19].

Biological context of Nts

• Thus, axotomy causes downregulation of several NT systems at the spinal level, suggesting that the possible effects of NT on primary sensory neurons is attenuated after peripheral axotomy [1].
• The presence of m4 receptor mRNA in only parts of the enkephalin, somatostatin, and neurotensin neuronal populations indicates that muscarinic receptor gene expression contributes to the functional and anatomical heterogeneity of the striatum that may relate to higher order of organization, including patch-matrix compartmentalization [20].
• Effects of intraventricular administration of neurotensin and somatostatin on thermoregulation in the rat [21].
• The specificity of endopeptidase 24.16 towards peptides of the tachykinin, opioid and neurotensin families was examined by competition experiments of tritiated neurotensin hydrolysis as well as HPLC analysis [22].
• Neurotensin 1 micrograms/ml accelerated the gastric emptying by 35% (p less than 0.02) [23].

Anatomical context of Nts

• After sciatic nerve transection, a marked decrease was observed in (1) the number of NT-R mRNA-positive neurons in DRGs, (2) NT mRNA-positive neurons in the dorsal horn, and (3) NT-IR cell bodies and fibers in laminae I-II [1].
• Enkephalin, neurotensin, and substance P immunoreactivite neurones of the rat GP following 6-hydroxydopamine lesion of the substantia nigra [24].
• Evidence for corticotropin-releasing factor, neurotensin, and somatostatin in the neural pathway from the central nucleus of the amygdala to the parabrachial nucleus [25].
• In this study we investigated the occurrence of enkephalin, neurotensin, and substance P immunoreactivity of the rat globus pallidus (GP) following lesion of the nigrostriatal pathway induced by the injection of the toxin 6-hydroxydopamine into the substantia nigra [24].
• Numerous retrogradely labeled neurons were found immunopositive for SOM in the periventricular and basolateral hypothalamus, many HRP-WGA labeled cells contained NT immunoreactivity in the ventral tegmental area, and TH-immunoreactive retrogradely labeled neurons were observed in both brain areas [26].

Associations of Nts with chemical compounds

• Our results showed that a lesion of the nigrostriatal pathway induced the expression of enkephalin, neurotensin, and substance P immunoreactivity in numerous pallidal cell bodies [24].
• Neurotensin and dopamine D2 activation oppositely regulate the same K+ conductance in rat midbrain dopaminergic neurons [27].
• Species differences in brain pre-pro-neurotensin/neuromedin N mRNA distribution: the expression pattern in mice resembles more closely that of primates than rats [28].
• Somatostatin as a mediator of the effect of neurotensin on pentagastrin-stimulated acid secretion in rats [29].
• The distributions of the top 20% of the terminal density range of NT, SP, AII and VIP support a classical medial/lateral division of the nucleus [30].

Physical interactions of Nts

• Identification of residues involved in neurotensin binding and modeling of the agonist binding site in neurotensin receptor 1 [31].
• The fact that the increase of mRNA parallels the appearance of labelled neurotensin in the substantia nigra indicates that the changes in the gene expression of tyrosine hydroxylase might be the consequence of the retrograde axonal transport of neurotensin [32].
• A study was done to determine if the Fos and neurotensin immunoreactivities elicited in the rat striatal complex by the selective dopamine D2 receptor antagonist, S(-)-eticlopride hydrochloride are co-localized in the same neurons [33].
• Finally, areas of dense [125I]neurotensin labeling often corresponded to zones previously shown to exhibit intense acetylcholinesterase staining, suggesting the existence of a possible link between the expression of neurotensin binding sites and that of acetylcholinesterase in certain neuronal populations [34].

Co-localisations of Nts

• Another subpopulation comprised larger neurons that exhibited intense neurotensin immunoreactivity in perikarya and proximal processes that was rarely co-localized with Fos immunoreactivity [35].

Regulatory relationships of Nts

• Haloperidol and neurotensin also suppress the excessive grooming induced by somatostatin but not that induced by SMS 201-995 [36].
• When injected concomitantly with TRH, SRIF blocked the response to TRH while ENK and NT both failed to affect the response to TRH [37].
• Neurotensin also significantly inhibited the elevations in glucagon, insulin, and somatostatin release induced by 20 mM arginine [38].
• Involvement of arachidonate metabolism in neurotensin-induced prolactin release in vitro [39].
• Intrathecal administration of the selective CCKB receptor antagonist L-365260 dose-dependently inhibited neurotensin hyperalgesia from the RMg (ID50 = 0.42 ng) at doses approximately 1000-fold less than that observed with the selective CCKA receptor antagonist devazepide (ID50 = 646 ng) [40].

Other interactions of Nts

• A significant percentage of CRF (54-66%)-, NT (40-53%)-, and SS (31-50%)-immunoreactive neurons were retrogradely labeled, predominantly within the lateral CNA [25].
• The distribution of NT-containing fibers was similar to the pattern of CCK-containing fibers and these were localized primarily to the central zone of the PBL [41].
• Numerous L-ENK-immunoreactive cell bodies, and moderate numbers of CCK-, NT-, and CRF-stained cell bodies were found in the AVPv [42].
• In conclusion, estrogens play a facilitatory role on NT-induced GH release in the rat, which is exerted through a mechanism independent of hypothalamic GHRH or somatostatin release [43].
• Changes of spinal substance P, calcitonin gene-related peptide, somatostatin, Met-enkephalin and neurotensin in rats in response to formalin-induced pain [44].

Analytical, diagnostic and therapeutic context of Nts

• Complementary distribution of receptors for neurotensin and NPY in small neurons in rat lumbar DRGs and regulation of the receptors and peptides after peripheral axotomy [1].
• In the second experiment, we analyzed portal plasma by high pressure liquid chromatography, and found that portal somatostatin-like immunoreactivity in blood collected during neurotensin infusion was composed of a single peak corresponding to somatostatin-14 [29].
• Histamine release was directly measured in in vivo skin blisters in rats in response to the intradermal injection of the peptide neurotensin (NT) [45].
• Levels of the neuropeptides substance P, somatostatin, and neurotensin were measured by radioimmunoassay in regions of the rat and human central nervous system (CNS) in aging [46].
• Effect of intraventricular injection of neurotensin and other various bioactive peptides on plasma immunoreactive somatostatin levels in rat hypophysial portal blood [47].

References