The effect of neurotensin on food consumption in the rat

Luttinger, Daniel; King, Richard A.; Sheppard, David N.; Strupp, John; Nemeroff, Charles B.; Prange, Arthur J.

doi:10.1016/0014-2999(82)90116-9

Cited by 111 publications

(92 citation statements)

References 13 publications

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“…Given the neuronal heterogeneity in the lateral hypothalamus, it is possible that the discriminating responses of the various peptide groups to peripheral signals may confer relative importance of physiological demands, such as delaying foraging to escape from a predator. When injected intracerebroventricularly, NT and hypocretin are anorectic and orexigenic, respectively (Luttinger et al, 1982;Haynes et al, 1999); however, both reinforce reward when endogenously released in the VTA (Felszeghy et al, 2007;Borgland et al, 2006). This dichotomy may enable animals in varied metabolic states to produce the behavioral response appropriate for the associated physiological demand.…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic Neurotensin Projections Promote Reward by Enhancing Glutamate Transmission in the VTA

et al. 2013

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The lateral hypothalamus (LH) sends a dense glutamatergic and peptidergic projection to dopamine neurons in the ventral tegmental area (VTA), a cell group known to promote reinforcement and aspects of reward. The role of the LH to VTA projection in reward-seeking behavior can be informed by using optogenetic techniques to dissociate the actions of LH neurons from those of other descending forebrain inputs to the VTA. In the present study, we identify the effect of neurotensin (NT), one of the most abundant peptides in the LH to VTA projection, on excitatory synaptic transmission in the VTA and reward-seeking behavior. Mice displayed robust intracranial self-stimulation of LH to VTA fibers, an operant behavior mediated by NT 1 receptors (Nts1) and NMDA receptors. Whole-cell patch-clamp recordings of VTA dopamine neurons demonstrated that NT (10 nM) potentiated NMDA-mediated EPSCs via Nts1. Results suggest that NT release from the LH into the VTA activates Nts1, thereby potentiating NMDA-mediated EPSCs and promoting reward. The striking behavioral and electrophysiological effects of NT and glutamate highlight the LH to VTA pathway as an important component of reward.

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Section: Discussionmentioning

confidence: 99%

Hypothalamic Neurotensin Projections Promote Reward by Enhancing Glutamate Transmission in the VTA

et al. 2013

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“…It is stored in secretory vesicles in enteroendocrine N cells in the intestine and in neuronal vesicles in the CNS. NT is released from the intestine in response to nutrient stimulation and may play a role in satiety regulation, as centrally administered NT decreases food intake in rodents (19,20). A few reports have shown that glucose stimulates NT secretion in healthy young humans (18) and from isolated perfused rat small intestine (4), but the underlying mechanisms of secretion are not well understood.…”

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confidence: 99%

Glucose stimulates neurotensin secretion from the rat small intestine by mechanisms involving SGLT1 and GLUT2, leading to cell depolarization and calcium influx

Kuhre

Bechmann

Albrechtsen

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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Kuhre RE, Bechmann LE, Wewer Albrechtsen NJ, Hartmann B, Holst JJ. Glucose stimulates neurotensin secretion from the rat small intestine by mechanisms involving SGLT1 and GLUT2, leading to cell depolarization and calcium influx. Am J Physiol Endocrinol Metab 308: E1123-E1130, 2015. First published April 21, 2015 doi:10.1152/ajpendo.00012.2015.-Neurotensin (NT) is a neurohormone produced in the central nervous system and in the gut epithelium by the enteroendocrine N cell. NT may play a role in appetite regulation and may have potential in obesity treatment. Glucose ingestion stimulates NT secretion in healthy young humans, but the mechanisms involved are not well understood. Here, we show that rats express NT in the gut and that glucose gavage stimulates secretion similarly to oral glucose in humans. Therefore, we conducted experiments on isolated perfused rat small intestine with a view to characterize the cellular pathways of secretion. Luminal glucose (20% wt/vol) stimulated secretion but vascular glucose (5, 10, or 15 mmol/l) was without effect. The underlying mechanisms depend on membrane depolarization and calcium influx, since the voltage-gated calcium channel inhibitor nifedipine and the KATP channel opener diazoxide, which causes hyperpolarization, eliminated the response. Luminal inhibition of the sodium-glucose cotransporter 1 (SGLT1) (by phloridzin) eliminated glucose-stimulated release as well as secretion stimulated by luminal methyl-␣-D-glucopyranoside (20% wt/vol), a metabolically inactive SGLT1 substrate, suggesting that glucose stimulates secretion by initial uptake by this transporter. However, secretion was also sensitive to GLUT2 inhibition (by phloretin) and blockage of oxidative phosphorylation (2-4-dinitrophenol). Direct K ATP channel closure by sulfonylureas stimulated secretion. Therefore, glucose stimulates NT secretion by uptake through SGLT1 and GLUT2, both causing depolarization either as a consequence of sodium-coupled uptake (SGLT1) or by closure of K ATP channels (GLUT2 and SGLT1) secondary to the ATP-generating metabolism of glucose.neurotensin; mechanisms of secretion; SGLT1; GLUT2 NEUROTENSIN (NT) is a 13-amino acid peptide neuromodulator, first isolated from bovine intestine and brain tissue (3,14). It is stored in secretory vesicles in enteroendocrine N cells in the intestine and in neuronal vesicles in the CNS. NT is released from the intestine in response to nutrient stimulation and may play a role in satiety regulation, as centrally administered NT decreases food intake in rodents (19,20). A few reports have shown that glucose stimulates NT secretion in healthy young humans (18) and from isolated perfused rat small intestine (4), but the underlying mechanisms of secretion are not well understood. Studies of secretion of the gut hormone glucagonlike peptide-1 (GLP-1) have indicated that glucose-stimulated secretion of this hormone involves electrogenic sodium uptake through sodium-glucose transporter 1 (SGLT1) as well as closure of ATP-sensitive potassium (K ATP ) channel...

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“…It has been suggested that xenin is released from a larger precursor, ␣-COP (coatomer protein complex subunit ␣), through posttranslational modification (4 -7). Xenin is structurally similar to neurotensin, which functions as a satiety factor by sharing an analogous COOH-terminal amino acid sequence (2,8,9). Similar to other anorectic gastrointestinal peptides, levels of circulating xenin increase after a meal, suggesting that xenin also may regulate food intake by acting as a satiety factor (2,10 -13).…”

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confidence: 99%

Xenin, a Gastrointestinal Peptide, Regulates Feeding Independent of the Melanocortin Signaling Pathway

et al. 2009

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OBJECTIVE-Xenin, a 25-amino acid peptide, was initially isolated from human gastric mucosa. Plasma levels of xenin rise after a meal in humans, and administration of xenin inhibits feeding in rats and chicks. However, little is known about the mechanism by which xenin regulates food intake. Signaling pathways including leptin and melanocortins play a pivotal role in the regulation of energy balance. Therefore, we addressed the hypothesis that xenin functions as a satiety factor by acting through the melanocortin system or by interacting with leptin. RESEARCH DESIGN AND METHODS-The effect of intracerebroventricular and intraperitoneal administration of xenin on food intake was examined in wild-type, agouti, and ob/ob mice. The effect of intracerebroventricular injection of SHU9119, a melanocortin receptor antagonist, on xenin-induced anorexia was also examined in wild-type mice. To determine whether the hypothalamus mediates the anorectic effect of xenin, we examined the effect of intraperitoneal xenin on hypothalamic Fos expression. RESULTS-Both intracerebroventricular and intraperitoneal administration of xenin inhibited fasting-induced hyperphagia inwild-type mice in a dose-dependent manner. The intraperitoneal injection of xenin also reduced nocturnal intake in ad libitum-fed wild-type mice. The intraperitoneal injection of xenin increased Fos immunoreactivity in hypothalamic nuclei, including the paraventricular nucleus and the arcuate nucleus. Xenin reduced food intake in agouti and ob/ob mice. SHU9119 did not block xenin-induced anorexia.CONCLUSIONS-Our data suggest that xenin reduces food intake partly by acting through the hypothalamus but via signaling pathways that are independent of those used by leptin or melanocortins. Diabetes 58:87-94, 2009

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The effect of neurotensin on food consumption in the rat

Cited by 111 publications

References 13 publications

Hypothalamic Neurotensin Projections Promote Reward by Enhancing Glutamate Transmission in the VTA

Hypothalamic Neurotensin Projections Promote Reward by Enhancing Glutamate Transmission in the VTA

Glucose stimulates neurotensin secretion from the rat small intestine by mechanisms involving SGLT1 and GLUT2, leading to cell depolarization and calcium influx

Xenin, a Gastrointestinal Peptide, Regulates Feeding Independent of the Melanocortin Signaling Pathway

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