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At least 19 recordsLinked to original sources
PubMed1986

Reproduction of postprandial neurotensin plasma levels by intravenous neurotensin and the effect of neurotensin on exocrine pancreatic secretion in humans.

A fatty meal releases neurotensin immunoreactivity from the small bowel in humans and dogs, and an infusion of synthetic neurotensin elicits exocrine pancreatic secretion in these species. It is not clear, however, which amount of exogenous neurotensin will reproduce endogenous neurotensin plasma levels as postprandial neurotensin immunoreactivity is composed of several fragments of neurotensin without biologic activity in addition to intact neurotensin. In order to clarify this question, we infused 1.25, 2.5, 5.0 and 7.5 pmol/kg/min synthetic Gln4-neurotensin in four volunteers, determined neurotensin plasma levels with a radioimmunoassay recognizing only intact neurotensin, and collected duodenal contents for estimation of pancreatic secretion. On another day, we determined neurotensin plasma levels after a fatty meal. Reverse-phase high-pressure liquid chromatography (HPLC) was performed on postprandial plasma samples. We found a stimulatory action of neurotensin on pancreatic secretion of volume enzymes and bicarbonate beginning with 1.25 pmol/kg/min neurotensin. The neurotensin plasma level after infusion of this dose of synthetic neurotensin was 69 pg/ml; after the meal, maximal neurotensin plasma concentration was 50 pg/ml (basal neurotensin plasma levels in both investigations were subtracted). HPLC indicated the presence of the tridecapeptide known to be the active molecular form of neurotensin in postprandial plasma. These results suggested that neurotensin plays a role as an endocrine hormone in the postprandial regulation of exocrine pancreatic secretion in humans.

Dietary Fats↗
PubMed2000

Comparative effects of neurotensin, neurotensin(8-13) and [D-Tyr(11)]neurotensin applied into the ventral tegmental area on extracellular dopamine in the rat prefrontal cortex and nucleus accumbens.

Ejections of 10(-5)-10(-3)M neurotensin into the ventral tegmental area increased dopamine efflux measured by electrochemical approaches in the prefrontal cortex of anaesthetized rats. In the same conditions, the effects evoked on dopamine efflux by 10(-5)M neurotensin(8-13) and [D-Tyr(11)]neurotensin were different from each other and depended on the explored area: the prefrontal cortex and the caudal and rostral nucleus accumbens. In the prefrontal cortex, neurotensin(8-13) was as potent as neurotensin, whereas [D-Tyr(11)]neurotensin was ineffective. In the caudal nucleus accumbens, when considering the initial intensity of the effect, neurotensin(8-13) and neurotensin appeared more potent than [D-Tyr(11)]neurotensin. In contrast, in the rostral nucleus accumbens, neurotensin(8-13) was less potent than [D-Tyr(11)]neurotensin and neurotensin. These results support the differential involvement of two pharmacologically distinct neurotensin receptor entities on ventral tegmental area neurons in the modulation of mesolimbic and mesocortical dopaminergic activity.

Animals↗
PubMed1988

Effect of neurotensin and its fragments neurotensin-(1-6) and neurotensin-(8-13) on dopamine release from cat striatum.

At low concentrations, neurotensin (10(-9) M) enhanced electrically evoked release of dopamine. At higher concentrations, neurotensin (10(-7) M) also enhanced basal release of dopamine. The carboxy-terminal sequence of neurotensin-(8-13) was fully active and enhanced both electrically evoked and basal release. In contrast, the amino-terminal fragment neurotensin-(1-6) did not enhance electrically evoked release of dopamine even at high concentrations (10(-6) M). However, it retained the ability to enhance basal dopamine release. Combination of different doses of apomorphine with a subthreshold (10(-10) M) and submaximal concentrations (10(-9) M) of neurotensin gave clear additive effects. It is concluded that in the cat striatum neurotensin stimulates dopamine release by a direct effect on its own neurotensin receptor, and does not modulate the sensitivity of presynaptic dopamine autoreceptors. Furthermore, it is suggested that there exist at least two types of neurotensin receptors in the cat striatum. One type stimulates evoked dopamine release and another influences basal release of dopamine.

Animals↗
PubMed1997

Effects of SR 48692 on neurotensin-induced calcium-activated chloride currents in the Xenopus oocyte expression system: agonist-like activity on the levocabastine-sensitive neurotensin receptor and absence of antagonist effect on the levocabastine insensitive neurotensin receptor.

The effect of the drug SR 48692 on the Ca(2+)-activated Cl- current induced by neurotensin on Xenopus oocytes injected with cRNAs encoding rodent high and low affinity neurotensin receptors, was examined. In this receptor expression system, SR 48692 failed to antagonize electrophysiological measurement of neurotensin-evoked current via the rat high affinity neurotensin receptor, whereas its application onto oocytes expressing the mouse low affinity neurotensin receptor triggered an inward current, as well as neurotensin itself. However, no current activation was observed after application of the drug on oocytes expressing the rat high affinity neurotensin receptor. These observations in the oocyte expression system did not reflect typical antagonist properties of SR 48692 drug.

Animals↗
PubMed1977

Mast cell binding of neurotensin. I. Iodination of neurotensin and characterization of the interaction of neurotensin with mast cell receptor sites.

Neurotensin was iodinated at equimolar concentrations of peptide, iodide, and chloramine-T, producing a labeled peptide with a specific activity of 1000 to 2000 Ci/mmol. Rat mast cells specifically and reversibly bound 1.27 pmol of neurotensin/10(6) cells with a reversible affinity, KD, of 154 nM. Optimum specific binding occurred betwen pH 6.8 and 7.2 under hypotonic conditions and dropped sharply as buffer concentration increased beyond 10 mM. The divalent cations Ca2+ and Mg2+ prevented binding with 50% inhibition at 1.5 and 4 mM, respectively. Binding was strongly and equally inhibited by the sodium and potassium salts of chloride, bromide, and iodide, and to a lesser degree by LiCl. Maximum binding of 125I-neurotensin occurred within 10 min at 0 degrees, and within 1.5 to 2 min binding was reduced to half-maximum in the presence of excess unlabeled neurotensin or upon 20-fold dilution in buffer. Both CaCl2 and NaCl were able to dissociate 60% of the total bound neurotensin: half the label bound was removed in 4 to 6 min. EDTA inhibited the binding only at high concentrations and no requirement was found for sulfhydryl groups, ATP, or a glycoprotein in the binding of neurotensin.

Animals↗
PubMed1983

Relation between lower esophageal sphincter (LES) pressure and the plasma concentration of neurotensin during intravenous infusion of neurotensin(1-13) and (Gln4)neurotensin(1-13) in man.

Ingestion of fat causes a pronounced decrease in lower esophageal sphincter (LES) pressure. This may be due in part to effects of neurotensin (NT), which is released postprandially after the ingestion of fat. The aim of the present investigation was to establish whether the LES pressure decreases at physiological plasma concentrations of NT(1-13). In addition, we have compared the effects and metabolism of NT(1-13) and (Gln4)NT(1-13). The experiments were performed in 3 healthy male volunteers who had fasted for at least 11 hours prior to the study. NT(1-13) or (Gln4)NT(1-13) were infused intravenously at a dose of 12 pmoles X kg-1 X min-1. LES pressure was monitored by a continuous pull-through method with a perfused catheter. The concentrations of chromatographically identified tridecapeptides were determined using NH2 and COOH-terminal directed antisera. Already one min after the start of the infusions the LES pressure had decreased by 43% of the control value. At that time the plasma concentration of the neurotensin tridecapeptide was about 15 pM. NT(1-13) and (Gln4)NT(1-13) had similar half-lives in plasma (2.5 min). NT(1-8) and (Gln4)NT(1-8) were found to be the main metabolites of NT(1-13) and (Gln4)NT(1-13) respectively. The results indicate that the increase in the plasma concentration of NT(1-13) seen after the ingestion of food is sufficient for neurotensin to function as a hormone of the endocrine type. NT(1-13) and (Gln4)NT(1-13) have the same effects on LES pressure in humans and show the same pharmacokinetic characteristics.

Adult↗
PubMed1998

Evidence for additional neurotensin receptor subtypes: neurotensin analogs that distinguish between neurotensin-mediated hypothermia and antinociception.

Neurotensin (NT), a tridecapeptide, is a neurotransmitter that elicits potent effects including hypothermia and antinociception in mice and rats. To date, there are two types of the neurotensin receptor (NTR) that have been molecularly cloned from the rat. However, several lines of evidence suggest the presence of additional NTR subtypes. We have identified a NT analog of the NT(8-13) fragment, NT27, that selectively causes only the hypothermic response in vivo, when microinjected into the periaqueductal gray (PAG) of rats. A dose of 18 nmol of NT or NT27 caused a body temperature lowering of 1.8 and 1.2 degrees C, respectively. This same dose of NT or NT27 yielded a hotplate maximum physiological effect of 75% and 25%, respectively. Interestingly, despite its high KD (620 nM) at the cloned NTR-1, NT27-I (the iodinated form of NT27) exerted a potent hypothermic effect even at a very low dose (0.6 nmol). Equally intriguing, was that NT24, a sterioisomer of NT27, with a much higher affinity (KD=0. 5 nM) at NTR-1, did not selectively induce hypothermia in mice, but did selectively induce hypothermia in rats.

Animals↗
PubMed1993

Xenopsin, neurotensin, neurotensin(8-13) and N-acetyl-neurotensin(8-13) inhibit vascular leakage in rats after tissue injury.

Swelling, edema and leakage of proteins from the vascular compartment are immediate inflammatory responses of living tissues to local injury. Xenopsin, neurotensin (NT), NT(8-13) and NAcNT(8-13) administered to male rats anesthetized with sodium pentobarbital 60 mg/kg i.p. inhibited swelling and edema in the paw induced by immersion in 58 degrees water for 1 min. The ED50 values for xenopsin. NT, NAcNT(8-13) and NT(8-13) for reducing heat-induced edema were 0.9, 1.5, 1.9 and 2.1 nmol/kg i.v., respectively. NAcNT(8-13) was chosen as a prototype for further studies because, compared to NT, it had minimal hypotensive effects. NAcNT(8-13), 4 nmol/kg i.v., injected 10 min before mechanical injury to muscle, produced by a 4 cm midline surgical incision in the rectus abdominis, or before freeze injury to the cortex, produced by applying a cold probe (-50 degrees C) to the skull for 4 min, reduced vascular leakage, measured as area of Monastral blue staining of the injured tissues. NAcNT(8-13), 4 nmol/kg i.v., also attenuated pulmonary edema induced by epinephrine bitartrate 10 micrograms/kg i.v. The ability of NAcNT(8-13) to inhibit vascular leakage was not linked to its transient hypotensive effects and it was not blocked by alpha-helical-CRF(9-41), a putative CRF receptor antagonist, or by chlorpheniramine, a H1-histamine receptor antagonist.

Animals↗
PubMed1991

Effects of neurotensin on midbrain dopamine neurons: are they mediated by formation of a neurotensin-dopamine complex?

The effects of neurotensin on midbrain dopamine neuron activity were studied in brain slices using single-unit recording techniques. At low concentrations (0.2-10 nM), neurotensin attenuated dopamine-induced inhibition without a significant effect on the basal firing rate. At higher concentrations (greater than 10 nM), however, it consistently caused an increase in cell activity. At even higher concentrations (greater than 100 nM), a sudden cessation of cell activity preceded by an increase in firing rate was observed. Whether this effect of neurotensin was due to depolarization inactivation or to a toxic effect of the peptide at high concentrations remains to be determined. To determine whether the effects of neurotensin were mediated by formation of a neurotensin-dopamine complex, several neurotensin analogues were studied. Neurotensin (8-13), which binds to both neurotensin receptors and dopamine, mimicked the effects of native neurotensin. Neuromedin N, which competes with neurotensin for the same receptor but does not bind to dopamine, also mimicked the effects. However, neurotensin (1-11), which forms a complex with dopamine but is inactive in competing for neurotensin receptors, was ineffective. In addition, the excitatory effect of neurotensin was not attenuated in the presence of dopamine receptor blockade by sulpiride. These results suggest that formation of a neurotensin-dopamine complex may not account for the action of neurotensin on dopamine cells. When combined with the fact that there is a high density of neurotensin receptors on dopamine cells, our results support the suggestion that the observed effects of neurotensin on dopamine neurons are most likely mediated by an activation of neurotensin receptors.

Animals↗
PubMed2004

Neurotensin depolarizes globus pallidus neurons in rats via neurotensin type-1 receptor.

The globus pallidus is a major component in the indirect pathway of the basal ganglia. There is evidence that neurotensin receptors exist in this nucleus. To determine the electrophysiological effects of neurotensin on pallidal neurons, whole-cell patch-clamp recordings were performed in the acutely prepared brain slices. Under current-clamp recordings, neurotensin at 1 microM depolarized pallidal neurons. Voltage-clamp recordings also showed an inward current induced by neurotensin. The depolarizing effect of neurotensin could be mimicked by the C-terminal fragment, neurotensin (8-13), but not by the N-terminal fragment, neurotensin (1-8). Both SR 142948A, a non-selective neurotensin receptor type-1 and type-2 antagonist, and SR 48692, a selective type-1 receptor antagonist, blocked the depolarizing effect of neurotensin, and which themselves had no effect on membrane potential. Thus, neurotensin type-1 receptors appear to mediate the effect of neurotensin. The depolarization evoked by neurotensin persisted in the presence of tetrodotoxin, ionotropic and metabotropic glutamate and GABA receptor antagonists, indicating that neurotensin excited the pallidal neurons by activating the receptor expressed on the neurons recorded. Current-voltage relationship revealed that both the suppression of a potassium conductance and the activation of a cationic conductance are involved in the neurotensin-induced depolarization. Based on the action of neurotensin in the globus pallidus we hypothesize that alterations of the striatopallidal neurotensin system contribute to symptoms of basal ganglia motor disorders.

Action Potentials↗
PubMed2005

Neurotensin and the neurotensin receptor-3 in microglial cells.

Microglia motility plays a crucial role in response to lesion or exocytotoxic damage of the cerebral tissue. The neuropeptide neurotensin elicited the migration of the human microglial cell line C13NJ by a mechanism dependent on both phosphatidylinositol-3 kinase (PI3 kinase) and mitogen-activated protein (MAP) kinases pathways. The effect of neurotensin on cell migration was blocked by the neurotensin receptor-3 propeptide, a selective ligand of this receptor. The type I neurotensin receptor-3 was the only known neurotensin receptor expressed in these microglial cells, and its activation led to the phosphorylation of both extracellular signaling-regulated kinases Erk1/2 and Akt. Furthermore, the effect of neurotensin on cell migration was preceded by a profound modification of the F-actin cytoskeleton, particularly by the rapid formation of numerous cell filopodia. Both the motility and the filopodia appearance induced by neurotensin were totally blocked by selective inhibitors of MAP kinases or PI3 kinase pathways. In the murine microglial cell line N11, the neurotensin receptor-3 is also the only neurotensin receptor expressed, and its activation by neurotensin leads to the phosphorylation of both Erk1/2 and Akt. In these cells, neurotensin induces the gene expression of several cytokines/chemokines, including MIP-2, MCP-1, interleukin-1beta and tumor necrosis factor-alpha. This induction is dependent on both protein kinases pathways. We observed that the effect of neurotensin on the cytokine/chemokine expression is also inhibited by the neurotensin receptor-3 propeptide. This is the demonstration that the neurotensin receptor-3 is functional and mediates both the migratory action of neurotensin and its induction of chemokines/cytokines expression.

Adaptor Proteins, Vesicular Transport↗
PubMed1999

Neurotensin depolarizes cholinergic and a subset of non-cholinergic septal/diagonal band neurons by stimulating neurotensin-1 receptors.

Identified cholinergic and a subtype of non-cholinergic, fast-firing neurons were recorded intracellularly in vitro from slices of guinea-pig brain. Recorded neurons were within the boundaries of the medial septum and vertical limb of the diagonal band of the forebrain. The effects of superfused neurotensin and neurotensin receptor antagonists were measured under single-electrode current clamp. Neurotensin consistently caused a dose-dependent, slow depolarization of cholinergic neurons that was accompanied by an increase in membrane resistance and a block of the long-duration (1-10 s) post-spike afterhyperpolarization when present. Neurotensin also blocked a shorter duration, slow afterhyperpolarization, but only in a minority of cholinergic neurons. When present, inhibition of the slow afterhyperpolarization changed the spike pattern from single spikes to short bursts. Inhibition of post-spike afterhyperpolarizations by neurotensin reversed more slowly than did other effects of neurotensin. Tetrodotoxin did not prevent the depolarizing effect of neurotensin. The non-selective neurotensin receptor antagonist, SR142948A, blocked the depolarizing effect of neurotensin but the low-affinity receptor antagonist, levocabastine, did not. A subgroup of noncholinergic, fast-firing neurons (23%) was also depolarized by neurotensin, an effect antagonized by SR142948A but not levocabastine. Neurotensin did not effect post-spike voltage transients or change the firing pattern of non-cholinergic neurons. These data suggest that neurotensin causes a slow depolarization and increased excitability of cholinergic and some noncholinergic neurons in an area of the brain that projects to the hippocampus. Neurotensin type 1 receptors appear to mediate these effects. Neurotensin may modulate hippocampal-dependent learning and memory processes through its effects on septohippocampal neurons.

Action Potentials↗
PubMed1998

Mesolimbic expression of neurotensin and neurotensin receptor during stress-induced gastric mucosal injury.

Neurotensin is a neurotransmitter present in the brain and gastrointestinal tract. Intracerebroventricular injection of neurotensin protects rats from gastric mucosal injury caused by cold water restraint (CWR). Direct injection of neurotensin into the nucleus accumbens (NACB), part of the mesolimbic dopamine system, reduces gastric mucosal injury, suggesting that neurotensin confers protection on the mucosa through interaction with the mesolimbic system. The hypothesis is that the concentration of neurotensin in the mesolimbic system decreases during CWR, affecting the expression of neurotensin and the neurotensin receptor. After 1 h of CWR, neurotensin concentration significantly decreased 41% in the NACB and returned toward control concentrations after 2 h of CWR. The concentration of neurotensin mRNA significantly decreased 46% after 1 h CWR and returned toward control after 2 h. In contrast, neurotensin binding sites in the NACB increased from 159 to 228 fmol/mg protein after 1 h of CWR and increased significantly to 280 fmol/mg protein after 2 h CWR, whereas the level of neurotensin receptor mRNA significantly decreased 51 and 50% at 1 and 2 h, respectively. These studies show that neurotensin concentration within the mesolimbic system is transiently reduced by CWR stress and that the number of neurotensin binding sites increases, presumably in response to the decrease in neurotensin.

Animals↗
PubMed1996

Neurotensin-containing endocrine cells and neurotensin receptor mRNA-expressing epithelial cells in the chicken thymus.

Distribution of neurotensin-containing cells and neurotensin receptor-expressing cells was examined in the chicken thymus using a combination of in situ hybridization histochemistry for neurotensin receptor mRNA and immunohistochemistry for neurotensin. Neurotensin receptor mRNA-expressing cells and neurotensin-immunoreactive cells were localized in the medulla. Neurotensin receptor mRNA-expressing cells showed a round or elongated shape, while neurotensin-immunoreactive cells revealed round, ovoid, spindle or reticular shapes. Neurotensin-immunoreactive cells were much more numerous than those displaying labeling for the neurotensin receptor mRNA in males and females. Furthermore, electron microscopic immunohistochemistry for neurotensin showed that immunoreactive cells contained a large number of round or spherical granules which were 250-350 nm in diameter. This evidence indicates that neurotensin is localized in endocrine cells, and that neurotensin receptor mRNA is expressed in epithelial cells. It further suggests the possibility of microenvironmental interaction of neurotensin between endocrine cells and epithelial cells within the chicken thymus.

Animals↗
PubMed1995

Neurochemical and behavioural effects of neurotensin vs [D-Tyr11]neurotensin on mesolimbic dopaminergic function.

Microinjection of neurotensin(1-13) or neurotensin(8-13) into the ventral tegmental area (VTA) of anaesthetized rats produced dose-dependent (1-100 pg) dopamine release in the nucleus accumbens as measured by differential pulse amperometry (DPA). Higher doses (100 pg-10 ng) of [D-Tyr11]neurotensin were required to produce an identical effect. In addition, the 3 peptides enhanced the K(+)-evoked [3H]DA release from nucleus accumbens slices. The stimulatory actions produced by 10(-8) M neurotensin(1-13) and neurotensin(8-13) were respectively of 96% and 72% while the effect of [D-Tyr11]neurotensin was only of 79% at 10(-6) M. Unilateral application of the 3 peptides in the VTA of cannulated rats produced contralateral circling. [D-Tyr11]neurotensin was effective in a dose-dependent manner, between 40 and 320 ng. Similar effects were observed with 80 ng of neurotensin(1-13) and neurotensin(8-13) in presence of the protease inhibitor thiorphan. In view of the higher potency of neurotensin(1-13) and neurotensin(8-13) versus [D-Tyr11]neurotensin to stimulate DA release both in vivo and in vitro and the higher efficacy of [D-Tyr11]neurotensin to induce circling, this study further strengthens the concept of neurotensin receptor heterogeneity.

Animals↗
PubMed1976

Synthesis and activities of neurotensin, and its acid and amide analogs: possible natural occurrence of [Gln4]-neurotensin.

It was considered, a priori, that the isolation of the tridecapeptide, neurotensin, might have inadvertently sllowed the hydrolysis of either the [Gln4]- or the [Leu13-NH2]-moieties. Neurotensin and its three acid and amide analogs, i.e., [Gln4]-neurotensin, neurotensin-NH2, and [Gln4]-neurotensin-NH2 were synthesized. Neurotensin and [Gln4]-neurotensin were indistinguishable by the hypotensive assay, hyperglycemic assay, contraction of the ileum, and radioimmunoassay. Neurotensin-NH2 and [Gln4]-neurotensin-NH2 showed less than 1% of these neurotensin activities. Present information does not elucidate whether the glutamic acid residue in position 4 of neurotensin in situ is present as Glu4 or as Gln4. At high levels, neurotensin released the luteinizing hormone, follicle stimulating hormone, and thyrotropin; [Gln4]-neurotensin-NH2 released thyrotropin, and [Gln4]-neurotensin released luteinizing hormone and follicle stimulating hormone, but these activities do not appear biologically significant.

Animals↗
PubMed1998

Neurotensin is an antagonist of the human neurotensin NT2 receptor expressed in Chinese hamster ovary cells.

The human levocabastine-sensitive neurotensin NT2 receptor was cloned from a cortex cDNA library and stably expressed in Chinese hamster ovary (CHO) cells in order to study its binding and signalling characteristics. The receptor binds neurotensin as well as several other ligands already described for neurotensin NT1 receptor. It also binds levocabastine, a histamine H1 receptor antagonist that is not recognised by neurotensin NT1 receptor. Neurotensin binding to recombinant neurotensin NT2 receptor expressed in CHO cells does not elicit a biological response as determined by second messenger measurements. Levocabastine, and the peptides neuromedin N and xenin were also ineffective on neurotensin NT2 receptor activation. Experiments with the neurotensin NT1 receptor antagonists SR48692 and SR142948A, resulted in the unanticipated discovery that both molecules are potent agonists on neurotensin NT2 receptor. Both compounds, following binding to neurotensin NT2 receptor, enhance inositol phosphates (IP) formation with a subsequent [Ca2+]i mobilisation; induce arachidonic acid release; and stimulate mitogen-activated protein kinase (MAPK) activity. Interestingly, these activities are antagonised by neurotensin and levocabastine in a concentration-dependent manner. These activities suggest that the human neurotensin NT2 receptor may be of physiological importance and that a natural agonist for the receptor may exist.

Amino Acid Sequence↗
PubMed2002

Probing the environment of neurotensin whilst bound to the neurotensin receptor by solid state NMR.

A functionally active analogue of neurotensin, neurotensin(8-13), has been observed whilst bound to the agonist-binding site of the rat neurotensin receptor by nuclear magnetic resonance (NMR). Through the application of slow magic angle sample spinning and high-power proton decoupling, sufficient resolution and sensitivity were obtained in the carbon-13 spectrum to allow an assignment of many of the side chain resonances arising from uniformly carbon-13/nitrogen-15-labelled neurotensin(8-13) whilst bound to the neurotensin receptor. Significant perturbations in carbon-13 chemical shift were observed upon the binding of the neurotensin(8-13) to the receptor. Most importantly significant shifts were observed in both the carboxy terminus and tyrosine side chain of the neurotensin(8-13), suggesting that these sites are important in the interaction of the neurotensin with the agonist-binding site on the neurotensin receptor. Conversely, no perturbations were observed for the carbon-13 sites within the guanidinium groups of the arginine side chains, indicating little interaction with the receptor-binding site, or a shielding of the local environment by the surrounding nitrogen atoms. These NMR observations lend further support to previous structure-activity studies, site-directed mutagenesis and modelling studies of the agonist-binding site of the neurotensin receptor, from which the same specific residues for which NMR perturbations were observed are important for neurotensin receptor activation by neurotensin.

Animals↗