脑血管病脑脊液神经降压素含量的改变

本研究测定21例正常对照组和68例脑血管病的脑脊液神经降压索含量。结果表明:(1)出血性脑血管病脑脊液神经降压素含量,比正常对照组显著增加;(2)缺血性脑血管病脑脊液神经降压素含量,比正常对照组显著减少。这提示,两类不同脑血管病脑脊液神经降压素含量,呈现明显的反向改变。     

侧脑室注射神经降压素对大鼠胰腺外分泌的影响

借助于胰腺插管,对麻醉大鼠的胰液分泌进行观察。通过埋植于脑内的注射套管,观察微量注射神经降压素对胰腺外分泌的影响。实验结果发现,侧脑室注射1ng、10ng、12.5ng神经降压素,可使胰腺分泌量、碳酸氢盐和蛋白质排出量明显增加。侧脑室注射50ng、100ng神经降压素时,胰液分泌量、碳酸氢盐和蛋白质排出量则降低。静脉灌流阿托品,可完全阻断10ng神经降压素刺激胰液分泌和部分阻断50ng、100ng神经降压素抑制胰液分泌的作用。表明,神经降压素刺激胰腺外分泌的中枢作用可能经胆碱能神经机制介导。     

神经降压素对大鼠胰岛B细胞损伤的预防作用

腹腔注射链佐霉素破坏大鼠胰岛B细胞以诱发糖尿病,注后24小时,血糖明显升高,血清及胰组织中胰岛素含量降低、其离体灌流的胰腺对高糖刺激的胰岛素释放反应也显著降低。10分钟前先给予神经降压素,对上述反应有明显的抑制作用,并具有量效关系。组织学检查证明,神经降压素预防注射可减轻链佐霉素对B细胞的损害。由于阿托品及酚妥拉明均可部分阻断神经降压素的这一作用,提示胆硷能M受体和肾上腺素能α受体可能参与神经降压素对B细胞的保护作用。     

胃溃疡患者手术治疗前后血浆神经降压素水平的变化

神经降压素（ＮＴ）是１９７３年由Ｃａｒｒａｗａｙ和Ｌｅｍａｎ从牛下丘脑中提取的一种生物活性多肽 ,以后发现ＮＴ也广泛存在于人和其它哺乳动物的脑和胃肠道中 ,因而是一种脑肠肽。文献指出［１］,ＮＴ具有强烈的扩张血管、降低血压和镇痛作用 ,还具有抑制胃液分泌、抑制胃肠运动和刺激胰液分泌、刺激肠粘膜分泌电解质等胃肠方面的作用。本文报告３４例胃溃疡手术治疗前后血浆神经降压素水平的变化。对象和方法一、对象 :（一）正常人 :３５人。均为我院保健科体检合格的健康人 ,无心、肝、肺、肾、胃肠道疾患 ,肝、肾功能试验正常。（…     

神经胶质瘤组织中神经肽Y和神经降压素的水平

神经肽Ｙ（ｎｅｕｒｏｐｅｐｔｉｄｅＹ,ＮＰＹ）和神经降压素（ｎｅｕｒｏｔｅｎｓｉｎ,ＮＴ）属于生物活性多肽物质,在哺乳动物脑组织中分布广泛,对心血管、消化系统及中枢神经系统具有较复杂的生物学效应。据文献报道,肾上腺嗜铬细胞瘤及人某些癌组织可有大量ＮＰ...     

颅内肿瘤与功能性头痛病人脑脊液神经降压素含量的比较

本实验采用放射免疫分析法测定了１０例伴头痛颅内肿瘤病人，１１例功能性头痛病人及８例正常人脑脊液内神经降压素含量。结果表明：（１）常见伴头痛的颅内肿瘤病人脑脊液神经降压素含量与正常人相比无明显改变。（２）功能性头痛病人头发病作时，脑脊液内神经降压素含量较正常人显著降低（Ｐ＜０．００１）。（３）颅内肿瘤与功能性头痛二组间脑脊液中神经降压素含量相比较呈非常显著差别（Ｐ＜０．００１），后者比前者明显降低。     

蛛网膜下腔注射神经降压素对大鼠血压和心率的影响

本文研究了蛛网膜下腔注射神经降压素（ｎｅｕｒｏｔｅｎｓｉｎ，ＮＴ）对大鼠血压和心率的影响，结果表明：注射ＮＴ后血压立即下降，继而有所回升，但不及正常水平，然后再次降低，持续６０ｍｉｎ；心率无明显改变。Ｈ１受体阻断剂苯海拉明能部分阻断ＮＴ的降血压效应，Ｈ２受体阻断剂甲氰咪胍无翻转作用。注射组胺释放剂Ｃｏｍｐｏｕｎｄ４８／８０使血压下降，待血压恢复正常水平后，再注射ＮＴ，其降压效应减弱。结果提示：蛛网     

大鼠息性心肌缺血后神经降压素的RIA

神经降压素(Neurotensin．NT)是一种体内分布较为广泛，并且有多种生物学效应的血管活性肽。它在体内可能作为一种神经递质、神经调质或神经激素而起作用。本实验通过结扎大鼠左冠状动脉前降支，造成急性心肌梗塞模型，观察结扎后不同时间血浆、部分脑区、垂体及心肌中神经降压素免疫活性物质(ir-NT)的含量变化。     

脑外伤大鼠血浆、肺中甘丙肽、神经降压素含量变化研究

目的:探讨脑外伤后发生急性肺损害时血浆、肺组织中甘丙肽、神经降压素含量变化及意义。 方法:通过放免法（RIA）测定大鼠脑外伤后血浆及肺组织甘丙肽、神经降压素含量。 结果: 脑外伤组血浆及肺组织甘丙肽、神经降压素含量均明显高于对照组，均P＜0.01。 结论: 血浆及肺组织甘丙肽、神经降压素含量增高可能是参与脑外伤后急性肺损伤过程中的重要因素。     

神经降压素在伤害性信息传递和调控中的作用

<正>神经降压素(neurotensin,NT)是由13个氨基酸组成的神经肽。在中枢神经系统内,NT作为神经递质或调质而发挥作用,其效应包括降温、镇痛、调节多巴胺能传递和刺激垂体前叶激素释放。目前己经发现并克隆的NT受体(NTR)有3种,其中NTR-1[1]和NTR-2[2]是有7次跨膜结构的G蛋白偶联受体,介导NT的信号传导;而NTR-3的功能尚不清楚。     

Neurotensin selectively facilitates glutamatergic transmission in globus pallidus

The tridecapeptide neurotensin has been demonstrated to modulate neurotransmission in a number of brain regions. There is evidence that neurotensin receptors exist in globus pallidus presynaptically and postsynaptically. Whole-cell patch-clamp recordings were used to investigate the modulatory effects of neurotensin on glutamate and GABA transmission in this basal ganglia nucleus in rats. Neurotensin at 1 microM significantly increased the frequency of glutamate receptor-mediated miniature excitatory postsynaptic currents. In contrast, neurotensin had no effect on GABA(A) receptor-mediated miniature inhibitory postsynaptic currents. The presynaptic facilitation of neurotensin on glutamatergic transmission could be mimicked by the C-terminal fragment, neurotensin (8-13), but not by the N-terminal fragment, neurotensin (1-8). The selective neurotensin type-1 receptor antagonist, SR48692 {2-[(1-(7-chloro-4-quinolinyl)-5-2(2,6-dimethoxyphenyl)pyrazol-3-yl)carbonylamino]-tricyclo(3.3.1.1.(3.7))-decan-2-carboxylic acid}, blocked this facilitatory effect of neurotensin, and which itself had no effect on miniature excitatory postsynaptic currents. The specific phospholipase C inhibitor, U73122 {1-[6-[[17beta-3-methoyyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione}, significantly inhibit neurotensin-induced facilitation on glutamate release. Taken together with the reported postsynaptic depolarization of neurotensin in globus pallidus, it is suggested that neurotensin excites the globus pallidus neurons by multiple mechanisms which may provide a rationale for further investigations into its involvement in motor disorders originating from the basal ganglia.     

Autoradiographic localization of [3H]neurotensin-binding sites in the hippocampal region of the rat and primate brain

The distribution of binding sites for the neuropeptide neurotensin was studied in the hippocampal region of the rat, monkey and human brain by using the method of in vitro receptor autoradiography. Biochemical studies of [3H]neurotensin binding to homogenates or sections of the rat hippocampal region showed it to be saturable, reversible and of high specificity. Displacement studies showed that neurotensin-(1-13) and neurotensin-(8-13) were active, while neurotensin-(1-6) and (1-8) were inactive in blocking the specific binding of [3H]neurotensin to hippocampal sections. The autoradiographic studies showed a highly heterogeneous pattern of [3H]neurotensin binding in the hippocampal region: the highest density was present in the entorhinal area while little binding was found in the Ammon's horn. In the rat most of the [3H]neurotensin binding was found in layer II of the medial entorhinal area and in the parasubiculum, while the lateral entorhinal area contained fewer [3H]neurotensin-binding sites. The laminar distribution of binding remained the same throughout the longitudinal axis of the entorhinal area. The pattern of [3H]neurotensin binding in the monkey resembled that seen in the rat inasmuch as the medial was rich and the lateral entorhinal area was poor in [3H]neurotensin-binding sites. In the medial entorhinal area most binding was found in layers I-IV. Unlike in the rat, the hilus of the monkey contained moderate and the molecular layer of the area dentata few [3H]neurotensin-binding sites. In the human brain the outer three layers of both the medial and the lateral entorhinal area contained binding sites for [3H]neurotensin. Binding sites for [3H]neurotensin were found also in the parasubiculum and in the molecular layer of the area dentata of the human brain. The present autoradiographic studies show that the hippocampal region of the rat and primate brain is rich in binding sites for [3H]neurotensin, that a majority of these are situated in the entorhinal area and that despite some differences in the regional distribution of these binding sites within the hippocampal region, some principal similarities may exist between these species.     

Cardiotropic effects of met-enkephalin and somatostatin under conditions of neurotensin receptor blockade

Pretreatment with the neurotensin receptor antagonist decreased the severity and time of Met-enkephalin-induced inhibition of vagal chronotropic effects in cats. The opiate receptor antagonist naloxone produced a delayed inhibitory effect on the synchronizing component of the vagal chronotropic effect under conditions of neurotensin receptor blockade. Cardiotropic effects of somatostatin remained unchanged during neurotensin receptor blockade. These data indicate one-way and two-way interactions between peptides modulating parasympathetic cardiac regulation.     

Serotoninergic mechanisms of the effects of neurotensin on passive avoidance behavior in rats

The aim of the present work was to identify the features of the actions of neurotensin on administration into the substantia nigra or dorsal cervical nucleus on the reproduction of passive avoidance reactions in rats. The results showed that the action of neurotensin administered into the substantia nigra was accompanied by sharp reductions in passive avoidance reactions, while administration into the dorsal cervical nucleus, conversely, led to increases in these reactions and slowing of their extinction. The effects of microinjections of the serotonin 5-HT(1A) receptor agonist 8-hydroxydipropylaminotetraline (8-OH-DPAT) into these brain structures were analogous to the effects of neurotensin. The different behavioral effects of administration of neurotensin corresponded to identifiable changes in the levels of serotonin and its metabolite 5-hydroxyindoleacetic acid in the caudate nuclei of the brain. These data led to the conclusion that the effects of neurotensin on passive avoidance behavior are associated with the regulation of the emotional state of the animals via actions on the functions of brain serotoninergic structures.     

Dipeptide Analog of Neurotensin Active Site Prevents the Development of Experimental Parkinson's Syndrome in Mice

Chronic administration of neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (30 mg/kg) to C57BL/6 mice caused death of all animals within 7 days. Dipeptide analog of neurotensin active site injected with this neurotoxin protected the mice from death even after 2-week intoxication. When younger mice and lower dose of neurotoxin (25 mg/kg) were used, all animals survived, but after 2 weeks they developed parkinsonian syndrome with muscular rigidity, akinesia, decrease in motor and explorative activities. In mice treated with dipeptide analog of neurotensin active site these manifestations of oligokinesia caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine were less pronounced and the corresponding parameters approximated the control values. Possible mechanisms of neuroprotective action of neurotensin active site analog are discussed.     

Neurotensin regulates intracellular calcium in ventral tegmental area astrocytes: evidence for the involvement of multiple receptors

Recent evidence suggests that some types of neurotensin receptors may be expressed by astrocytes. In order to explore the function of neurotensin receptors in astrocytes, the effect of a neurotensin receptor agonist, neurotensin(8-13), on intracellular Ca(2+) dynamics in mixed neuronal/glial cultures prepared from rat ventral tegmental area was examined. It was found that neurotensin(8-13) induces a long-lasting rise in intracellular Ca(2+) concentration in a subset of glial fibrilary acidic protein-positive glial cells. This response displays extensive desensitization and appears to implicate both intracellular and extracellular Ca(2+) sources. In the absence of extracellular Ca(2+), neurotensin(8-13) evokes only a short-lasting rise in intracellular Ca(2+). The neurotensin-evoked intracellular Ca(2+) accumulation is blocked by the phospholipase C inhibitor U73122 and by thapsigargin, suggesting that it is initiated by release of Ca(2+) from an inositol triphosphate-dependent store. The Ca(2+)-mobilizing action of neurotensin(8-13) in astrocytes is dependent on at least two receptors, because the response is blocked in part only by SR48692, a type 1 neurotensin receptor antagonist, and is blocked completely by SR142948A, a novel neurotensin receptor antagonist. The finding that the type 2 neurotensin receptor agonist levocabastine fails to mimic or alter the effects of neurotensin(8-13) on intracellular Ca(2+) makes it unlikely that the type 2 neurotensin receptor is involved.In summary, these results show that functional neurotensin receptors are present in cultured ventral tegmental area astrocytes and that their activation induces a highly desensitizing rise in intracellular Ca(2+). The pharmacological profile of this response suggests that a type 1 neurotensin receptor is involved but that another, possibly novel, non-type 2 neurotensin receptor is also implicated. If present in vivo, such signalling could be involved in some of the physiological actions of neurotensin.     

Non-neuronal excitatory neurotensin receptors on the taenia coli of the guinea pig: lack of influence of tetrodotoxin and dynorphin

Picomoles of neurotensin caused contractions of the smooth muscles of the taenia coli and the myenteric plexus preparation of the guinea pig ileum. The musculotropic effect of neurotensin on the taenia coli was resistant to tetrodotoxin and to treatment with dynorphin. In contrast, the contractile activity of the neuropeptide in the ileum was substantially modified by pretreatment with tetrodotoxin or dynorphin. It is concluded that, whereas neurotensin causes a direct muscular response on the taenia coli via activation of selective peptide receptors probably located on the muscle membrane, the neuropeptide causes a predominant indirect action on the ileum mediated apparently via the release of acetylcholine from the nerve terminals of the myenteric plexus. Neurotensin may play a role in the control of gut peristalis either by modifying the release of neurotransmitters or by directly influencing the smooth muscles of the intestines.     

Effects of neurotensin and neurotensin analogues on the migrating myoelectrical complexes in the small intestine of rats

The purpose of the present experiments was to study the effect of neurotensin and neurotensin analogues on the migrating myoelectrical complexes in the small intestine of rats. Four bipolar electrodes were implanted into the muscular wall of the small intestine. The electrodes were placed 5, 15, 25 and 35 cm distal to the pylorus. 7–10 days after the operation the animals were fasted for 48 h with free access to water. Some experiments were performed on conscious rats and in others the rats were anesthetized with pentobarbital, 30 mg/kg. I.v. infusion of either neurotensin (NT) or (Gln⁴)-neurotensin at doses of 1.8, 3.6 and 7.1 pmol kg^-1· min^-1abolished the migrating myoelectric complexes, which were replaced by increased spiking activity along the whole length of the small intestine from which activity was recorded. The changes in myoelectrical activity were observed within 2–4 min after commencement of the infusion. The activity returned to control levels within 5–15 min after the end of the infusion period. The neurotensin sequences NT 9–13, NT 8–13, NT 4–13, NT 1–9 and (Gln⁴)-NT 1–11 did not induce any changes in the electrical activity in the small intestine. The effects of NT and (Gln⁴)-neurotensin on the myoelectrical activity in the small intestine were indistinguishable. The changes induced by NT or (Gln⁴)-NT resemble those found after the ingestion of food. The present data indicate that the intact NT sequence, rather than smaller NT fragments, is necessary to induce changes in myoelectrical activity in the small intestine.     

A study of the concentrations of substance P and neurotensin in the gastrointestinal tract of various mammals

Immunoreactive substance P and neurotensin in extracts of the digestive tract of man, cat, guinea-pig, pig, rabbit, and rat were measured by radioimmunoassay using antisera directed against the C-terminal portions of the two peptides. In all species except the cat, the concentrations of substance P were highest in the small intestine, intermediate in the large intestine and lowest in the stomach and oesophagus: the digestive tract of the cat displayed a rather even distribution of substance P. As observed in the ileum of guinea-pig, rabbit, and rat, the external muscle layer including the myenteric plexus contained 2-5 times higher concentrations of substance P than the whole ileal wall, whereas the substance P concentrations in the mucosa were only about one sixth of those in the whole wall. High performance liquid chromatography of extracts of human, feline and rabbit ileum showed that all the immunoreactive substance P eluted at the positions of substance P and substance P sulfoxide. The distribution of immunoreactive neurotensin along the digestive system of all six species was very similar. The highest concentrations of neurotensin were measured in the distal part of the small intestine, whereas the large intestine, stomach and oesophagus contained only low concentrations of neurotensin relative to the concentrations in the ileum. As examined in the ileum of guinea-pig, rabbit, and rat, the mucosa exhibited 2.5-4 times higher concentrations of neurotensin than the whole ileal wall, while the concentrations of neutrotensin in the external muscle layer including the myenteric plexus were only 4-20% of those in the whole wall. High performance liquid chromatography of the immunoreactive neurotensin extracted from the cat ileum yielded a single peak corresponding to neurotensin while the immunoreactive neurotensin extracted from the ileum of man and rabbit was eluted in two peaks, 55 and 72% of the recovered immunoreactivity, respectively, corresponding to neurotensin. These findings are in line with the proposed roles of substance P in the neural, and neurotensin in the endocrine, control and maintenance of gastrointestinal motility.