Neurotensin: central nervous system effects of a neuropeptide

Nemeroff, Charles B.; Luttinger, Daniel; Prange, Arthur J.

doi:10.1016/0166-2236(80)90080-6

Cited by 90 publications

(22 citation statements)

References 12 publications

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“…Peptide receptors are overexpressed on various cancer cells and represent attractive targets for tumour imaging and therapy. Over-expression of NT receptors has been reported in breast, pancreatic, prostate, lung and colon cancers [3][4][5][6]. Peptide-based conjugates consisting of NT analogues linked to radionuclides could be interesting radiopharmaceuticals to selectively deliver radionuclides to receptor-expressing tumour cells.…”

Section: Therapy Studiesmentioning

confidence: 99%

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A stable neurotensin-based radiopharmaceutical for targeted imaging and therapy of neurotensin receptor-positive tumours

García-Garayoa

Bläuenstein

Blanc

et al. 2008

Eur J Nucl Med Mol Imaging

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Purpose Neurotensin (NT) and its high affinity receptor (NTR1) are involved in several neoplastic processes. Thus, NT-based radiopharmaceuticals are potential tracers for targeted diagnosis and therapy of NTR-positive tumours. A new analogue based on NT(8-13), NT-XIX, with the three enzymatic cleavage sites stabilised, was synthesised and tested. Methods The synthesis was performed by Boc strategy. Labelling with 99m Tc/ 188Re was performed using the tricarbonyl technique. Metabolic stability was tested in vitro and in vivo. NT-XIX was further characterised in vitro in HT-29 cells and in vivo in nude mice with HT-29 xenografts. Results NT-XIX showed much longer half-lives than nonstabilised analogues. Binding to NTR1 was highly specific, although the affinity was lower than that of natural NT. Bound activity rapidly internalised into HT-29 cells and 50% remained trapped after 24 h. In the time-course biodistribution, the highest uptake was found in the tumour at all p.i. times. In vivo uptake was specific, and accumulation of activity in the kidneys was low. Radioactivity clearance from healthy organs was faster than that from the tumour, resulting in improved tumour-to-tissue ratios and good SPECT/CT imaging. Treatment with 188 Re-NT-XIX (30 MBq, in three or four fractions) decreased tumour growth by 50% after 3 weeks. Conclusion The high in vivo stability and the favourable in vivo behaviour makes NT-XIX an excellent candidate for the imaging and therapy of NTR1-positive tumours.

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Section: Therapy Studiesmentioning

confidence: 99%

“…It fulfils a dual function: neurotransmitter or neuromodulator in the nervous system and local hormone in the periphery [6,7]. Three NTR subtypes havereceptors, whereas NTR3 is a single trans-membrane domain type I receptor, showing homology with sortilin [9].…”

Section: Introductionmentioning

confidence: 99%

A stable neurotensin-based radiopharmaceutical for targeted imaging and therapy of neurotensin receptor-positive tumours

García-Garayoa

Bläuenstein

Blanc

et al. 2008

Eur J Nucl Med Mol Imaging

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“…In the central nervous system NT participates in the regulation of a variety of physiological and behavioral processes [3,4]. Its peripheral activities include hypotension, inhibition of gastric acid secretion, stimulation of ileum contraction, vasodilation, increase in vascular permeability and mast cell degranulation [1,3].…”

Section: Introductionmentioning

confidence: 99%

Neurotensin modulates human neutrophil locomotion and phagocytic capability

Goldman¹,

Bar‐Shavit²,

Romeo³

1983

FEBS Letters

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Neurotensin (NT) was found to induce oriented locomotion and augment the phagocytic capability of human blood neutrophils over lo-"-lo-' M. The tridecapeptide also causes Ca2* extrusion from neutrophils, very likely as a result of intracellular Ca2+ mobilization. It is suggested that the NT-mediated functional modulation of neutrophils correlates with the capacity of NT to affect the i'~tracellular compartmentalization of Ca 2+ . Peripheral NT-elicited phenomena such as vasodilation, enhanced vascular permeability, mast cell degranulation and the enhancement of directional migration and phagocytosis of neutrophils described here, classify NT as a typical mediator of inflammation. NeutrophilNeurotensin Chemotaxis

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“…TRH and neurotensin have also been reported to exhibit mutually antagonist effects (Nemeroff et al 1980). The behavioural actions of both peptides have been investigated in three test systems: locomotor activity after injection in NA, shaking behaviour after injection in PAG and changes induced by PAG injection in response time to a nociceptive stimulus.…”

Section: Ppproceedings Of Thementioning

confidence: 99%

“…The neuropeptides neurotensin and thyrotrophin-releasing hormone (TRH) are widely distributed in the brain, with high concentrations of both in nucleus accumbens (NA) and periaqueductal grey region (PAG) (Hokfelt, Fuxe, Johansson, Jeffcoate & White, 1975;Nemeroff, Luttinger & Prange, 1980). TRH and neurotensin have also been reported to exhibit mutually antagonist effects (Nemeroff et al 1980).…”

Section: Ppproceedings Of Thementioning

confidence: 99%

Communications

1981

The Journal of Physiology

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Neurology, Queen Square, LondonBiochemical data suggest that L-glutamate (L-glu) and L-aspartate (L-asp) could be the neurotransmitters of the parallel and the climbing fibres respectively in the mammalian cerebellum. We have now used in vitro sagittal slices of adult rat cerebellum to study the responses of Purkinje cells (PCs) to ionophoretic applications of L-glu and L-asp in the molecular layer.Extra-and intra-cellular recordings were made from eighty PCs and L-glu and L-asp were released into their dendritic fields by short current pulses (5 to 100 msec) through a separate multibarelled electrode filled with 0 5 M salt solutions of the drugs.In the nineteen cells recorded from intracellularly, transient depolarizations up to 17 mV in amplitude and with depolarizing slopes up to 0 4 mV/msec were evoked by 2 to 10 nC L-glu or L-asp applied in the molecular layer. Maximum sensitivities were 8 mV/nC for L-glu and 6-4 mV/nC for L-asp. These depolarizations were accompanied by no change in cell input resistance, whereas steady applications of high doses of L-asp or L-glu decreased the membrane resistance.In the extracellularly recorded cells, the lowest threshold for L-glu or L-asp mediated excitations of PCs was as low as 25 pC, with a latency for the response as short as 7 msec. The mapping of these excitatory responses confirmed that the sensitivity of the dendrites for L-glu was greater than that of the soma (Chujo, Yamada & Yamamoto, 1975), and we showed in addition that the same was true for L-asp. No differential sensitivity of PC dendrites for L-asp and L-glu was detected in 66 0 of the tested cells; in the remainder, the sensitivity for L-asp declined markedly in the upper third of the molecular layer, whereas it remained high for L-glu.Finally, the agonist quisqualic acid was a much more potent excitant of PCs than L-glu or L-asp when applied in their dendritic fields, whereas the other major agonist N-methyl DL-aspartate (Sigma) only produced a very weak excitatory effect under the same conditions. The excitatory effects of L-asp, L-glu and quisqualic acid on PCs were antagonized by L-glutamic acid diethyl ester more consistently than by D-a amino adipate, suggesting, together with the previous observations, that L-asp and L-glu act on PCs via quisqualic acid receptors rather than via N-methyl D-aspartate receptors.

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Neurotensin: central nervous system effects of a neuropeptide

Cited by 90 publications

References 12 publications

A stable neurotensin-based radiopharmaceutical for targeted imaging and therapy of neurotensin receptor-positive tumours

A stable neurotensin-based radiopharmaceutical for targeted imaging and therapy of neurotensin receptor-positive tumours

Neurotensin modulates human neutrophil locomotion and phagocytic capability

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