CCK—8翻转k-受体激动剂U50488H对急性分离大鼠背根神经节神经元上钙通道的抑制效应

实验以急性分离的大鼠背根神经节（ＤＲＧ）神经元为标本，用全细胞膜片钳（ｗｈｏｌｅ—ｃｅｌｌｐａｔｃｈ－ｃｌａｍｐ）方法记录钙通道电流，观察分析特异性。受体激动剂Ｕ５０４８８Ｈ对电压依赖性钙通道电流的作用，和ＣＣＫ—８对Ｕ５０４８８Ｈ作用的影响，及其受体机制、结果表明，Ｕ５０４８８可明显抑制钙通道电流，其抑制作用可被。受体桔抗剂Ｎｏｒ—ＢＮ１或ＣＣＫ—８所翻转，而ＣＣＫ－８的作用又可被ＣＣＫ—８受体拮抗剂Ｌ３６５，２６０所对抗。但ＣＣＫ—８本身对钙通道电流并无增强作用，反有轻微的抑制作用。由此得出结论。ＣＣＫ－８可经ＣＣＫ—８受体对抗Ｋ受体介导的对钙通道电流的抑制作用。     

惊恐障碍时淋巴细胞CCK－8浓度

惊恐障碍时淋巴细胞ＣＣＫ－８浓度［英］／ＢｒａｍｂｉｌｌａＦ…∥ＡｍＪＰｓｙｃｈｉａｔｒｙ．－１９９３，１５０（７）；１１１１～１１１３在外周注入缩胆囊素四肽（ＣＣＫ－４）会引起健康者及惊恐障碍患者惊恐发作。由于外周间隙缩胆囊素的分泌能反映中枢产生的...     

长时间电针时大鼠脑内八肽胆囊收缩素的生成和释放加速

本文用大鼠进行实验，观察了长时间电针刺激时脑脊液中和中脑层水周围灰质内ＣＣＲ－８样免疫活性物质（ＣＣＫ－８－ｉｒ）含量，并用Ｎｏｒｔｈｅｒｎ印迹法测定脑内ＣＣＫｍＲＮＡ含量的变化，结果表明，电针１ｈ后大鼠脑脊液中ＣＣＫ－８－ｉｒ的浓度增高，２ｈ后中脑导水管周围灰质的含量也明显升高，８ｈ后大鼠脑内ＣＣＫ－８ｍＲＮＡ含量显著增加，表明长时间电针加速脑内ＣＣＫ－８的生成和释放，最终加速了ＣＣＫ基因表达，     

贪食症患者脑脊液CCK－8浓度

贪食症患者脑脊液ＣＣＫ－８浓度［英］／ＬｕｄｉａｒｄＲＢ…∥ＡｍＪＰｓｙｃｈｉａｔｒｙ．－１９９３，１５０（７）；１０９９～１１０１缩胆囊素（ＣＣＫ）是一种以不同形式存在的神经活性肽，对外周及中枢神经系统具有多种作用。有研究提示中枢神经系统ＣＣＫ和苯...     

不同氨基酸受体拮抗剂对缺血纹体CCK—8释放的影响

目的：研究不同兴奋性氨基酸受体拮抗剂（ＭＫ８０１，Ｓｐｅｒｍｉｎｅ，ＤＮＱＸ）对大鼠脑缺血时纹体缩胆囊肽－８（ＣＣＫ－８）释放的影响。方法：用微透析和ＲＩＡ法测定半球缺血时纹体ＣＣＫ－８的释放。结果：脑缺血时纹体ＣＣＫ－８释放明显增高，缺血前分别给予三种拮抗剂，都明显地降低缺血时纹体ＣＣＫ－８的不正常释放。结论：表明脑缺血时的ＣＣＫ－８和兴奋性氨基酸（ＥＡＡ）之间有协同的相互作用，抑制ＣＣＫ－８释放增高，可能是兴奋性氨基酸受体拮抗剂保护缺血大脑的机制之一。     

胆囊收缩素的抗惊厥作用

胆囊收缩素（ＣＣＫ）不仅是一个胃肠道激素，而且也是十分重要的中枢神经递质，同时具有调质的作用。研究证明，胆囊收缩素是一个重要的抗惊厥物质。本文对近年来ＣＣＫ与癫痫关系的研究进展进行阐述，主要包括ＣＣＫ的生物学特征、痫性发作诱导ＣＣＫ的表达，以及ＣＣＫ的抗惊厥作用和可能机制等。     

氟哌啶醇治疗后精神分裂症脑脊液CCK—8变化

应用放射免疫法测定８例精神分裂症患者及其性别、年龄配对的正常人脑脊液（ＣＳＦ）８肽胆囊收缩素（ＣＣＫ—８）的免疫反应活性，观察了患者在氟哌啶醇治疗６周后ＣＳＦ中ＣＣＫ—８免疫反应活性的变化，以及他们治疗前后２４小时尿ＭＨＰＧ排泄量的变化。结果发现，患者基础状态下ＣＳＦＣＣＫ—８显著低于与其性别、年龄配对的正常人。经６周氟哌啶醇治疗后患者ＣＳＦＣＣＫ—８显著增高，接近正常对照组。治疗前ＣＳＦＣＣＫ—８与ＳＡＮＳ评分呈显著负相关，而与ＳＡＰＳ评分呈显著正相关。正常对照组及患者治疗后的ＣＳＦＣＣＫ—８免疫反应活性与年龄皆呈高度正相关。文章就精神分裂症与ＣＳＦＣＣＫ—８的关系进行了讨论     

丙咪嗪拮抗CCK－4的致惊恐作用

丙咪嗪拮抗ＣＣＫ－４的致惊恐作用【英】／ＢｒａｄｗｅｊｎＪ…ＡｍＪＰｓｙｃｈｉａｔｒｙ─１９９４，１５１（２）；─２６１～２６３缩胆囊素四肽（ＣＣＫ－４）是中枢神经系统的一种神经递质，能促发人的惊恐发作。近来研究发现惊恐障碍可能继发于ＣＣＫ系统神经生...     

CCK—8及损毁MFB对腹侧被盖区和伏核多巴胺,CCK—8含量的影响

应用荧光分光光度法和放射免疫法，在以６－羟基多巴胺（６－ＯＨＤＡ）单侧损毁内侧前脑束（ＭＦＢ）制备的偏侧帕金森病（ＰＤ）大鼠模型身上，测定了腹侧被盖区（ＶＴＡ）和伏核（Ａｃｂ）中多巴胺（ＤＡ）和八胺胆囊收缩素（ＣＣＫ－８）的含量，并测定了ＴＶＡ和Ａｃｂ区微量注射ＣＣＫ－８对正常大鼠ＤＡ含量的影响。结果如下：ＰＤ大鼠模型损毁侧ＶＴＡ和Ａｃｂ的ＤＡ和ＣＣＫ－８的含量与健康及对照组相比均减少（Ｐ〈０．０     

T细胞亚群及粘附分子在实验性变态反应性神经炎中的作用

目的探讨Ｔ细胞亚群及粘附分子在实验性变态反应性神经炎（ＥＡＮ）中的作用。方法用兔坐骨神经匀浆免疫Ｗｉｓｔａｒ大鼠，建立ＥＡＮ模型；同时用抗细胞间粘附分子－１（ＩＣＡＭ－１）单抗注入大鼠后再诱导ＥＡＮ。观察自然病程组、抗体注射组及对照组动物的临床病理。用双重酶标免疫组化技术检测ＣＤ４＋、ＣＤ８＋Ｔ细胞分布以及粘附分子ＣＤ５４、ＣＤ１１ａ、ＣＤ６２在ＣＤ４＋及ＣＤ８＋细胞上的表达。结果抗体注射组发病率及发病程度明显低于自然病程组；组织中粘附分子在ＣＤ４＋细胞上的表达及ＣＤ４＋／ＣＤ８＋自然病程组高于抗体注射组；ＣＤ５４、ＣＤ１１ａ在ＣＤ４＋细胞上的表达高于ＣＤ８＋细胞。结论ＣＤ４＋细胞是主要的效应细胞，ＣＤ４＋细胞上粘附分子的表达对效应Ｔ细胞进入病变组织起主导作用；抗ＩＣＡＭ－１抗体能够预防ＥＡＮ发生。     

Is cholecystokinin octapeptide (CCK-8) a candidate for endogenous antiopioid substrates?

Cholecystokinin octapeptide (CCK-8), given intracerebroventricularly (icv) or intrathecally (ith) at the dose range of 0.25-4.0 ng, dose-dependently antagonised the effect of morphine analgesia and electroacupuncture analgesia (EAA) in the rat. That CCK-8 antiserum was capable of reversing the tolerance to EAA and changing the non-responders of EAA into responders suggest CCK-8 to be the endogenous anti-opioid substrate and that blocking the effect of CCK-8 may prove to be a powerful way of augmenting the effect of morphine analgesia and EA analgesia.     

Electrophysiological effects of cholecystokinin octapeptide on identified rat nigrostriatal dopaminergic neurons

Cholecystokinin octapeptide (CCK-8) exists in a subpopulation of midbrain dopaminergic (DA) neurons and has been shown to affect the activity of unidentified DA cells. This study describes the effects of the sulfated (CCK-8S) and unsulfated (CCK-8US) peptides (8 micrograms/kg, i.v.) on the ability of apomorphine to inhibit the firing rate of nigrostriatal DA cells identified by antidromic activation from the caudate nucleus of anesthetized rats. CCK-8S excited 9/25 DA cells while CCK-8US was without effect on firing rate (n = 9). CCK-8S pretreatment resulted in complex changes in the sensitivity of nigrostriatal DA cells to apomorphine which were related to whether an initial excitatory response was elicited by CCK-8S. CCK-8US did not alter apomorphine sensitivity. These results suggest that CCK-8S can exert modulatory effects on DA cells independent of a direct excitatory action. The effect of acute CCK-8 injection on the number of spontaneously active DA cells in stereotaxically defined regions of the substantia nigra and ventral tegmental area was also determined. CCK-8S doubled the number of active cells in these areas; CCK-8US did not alter the population activities.     

Effects of cholecystokinin-related peptides on self-stimulation behaviour in rats

The effects of cholecystokinin octapeptide sulfate ester (CCK-8-SE), its N-terminal tripeptide (CCK-2-4-SE) and its C-terminal tetrapeptide (CCK-5-8) were investigated on hypothalamic self-stimulation in rats. CCK-8-SE and CCK-5-8 in 400 pmole doses inhibited self-stimulation behaviour, while CCK-2-4-SE was ineffective. In 80 pmole doses the peptides showed no effect. It is suggested that CCK-5-8 itself influences self-stimulation behaviour.     

Cataleptogenic and anticataleptic activity produced by cholecystokinin octapeptides in mice

The catalepsy induced by subcutaneously (sc.) and intracerebroventricularly (icv.) administered cholecystokinin octapeptide sulfate ester (CCK-8-SE) and desulfated cholecystokinin octapeptide (CCK-8-NS), and the effects of CCK-8-SE and CCK-8-NS on haloperidol-induced catalepsy, were investigated in mice. The results demonstrate the bimodal effect of CCK octapeptides in a catalepsy test. With sc. administration CCK-8-SE in the doses of 0.4 or 0.8 mumole/kg, but not CCK-8-NS at any dose, induced catalepsy. Furthermore, the catalepsy induced by CCK-8-SE was of short duration. With icv. administration only 40 pmole CCK-8-NS induced significant catalepsy. When 0.2, 0.4 and 0.8 mumole/kg sc. doses of CCK-8-NS or 0.4 pmole icv. dose of CCK-8-SE or CCK-8-NS was given in combination with intraperitoneal (ip.) administration of 1.0 mg/kg haloperidol, the total duration of catalepsy was suppressed. Finally, CCK-8-SE sc. when given in combination with haloperidol ip., exerted a biphasic, synergistic-antagonistic effect on the haloperidol-induced catalepsy.     

Cholecystokinin octapeptides influence tolerance to ethanol in mice

The effects of graded doses of cholecystokinin octapeptide sulphate (CCK-8-S) and non-sulphated CCK-8 (CCK-8-NS) on the development of tolerance to the hypothermic effect of ethanol were investigated in mice. The animals were pretreated with daily doses of CCK-8-S, CCK-8-NS (0.003-30 nmol/animal s.c.) or vehicle, followed two hours later by the i.p. administration of ethanol (4 g/kg). The same treatments were repeated on three consecutive days. The hypothermic response to ethanol administration gradually diminished, this phenomenon being accepted as indicating the development of tolerance to ethanol. Both CCK-8-S and CCK-8-NS inhibited the development of tolerance. While CCK-8-S resulted in a linear dose-response effect (0.3-30 nmol/animal), CCK-8-NS gave rise to a bell-shaped curve with effective blocking doses of 0.3-3 nmol/animal. There was no difference in colonic temperature between peptide and vehicle-treated, ethanol-naive animals, indicating that the peptide did not change the initial sensitivity to ethanol.     

Cholecystokinin/opioid interactions

Cholecystokinin (CCK) acts as an anti-opioid peptide. The mechanisms of CCK-opioid interaction under normal and pathological conditions were examined with various techniques. Nerve injury induces upregulation of CCK mRNA and CCK2 receptors in sensory neurons. The involvement of CCK in spinal nociception in normal and axotomized rats was examined. The CCK2 receptor antagonist CI-988 did not reduce spinal hyperexcitability following repetitive C-fiber stimulation in normal or axotomized rats, suggesting that CCK is probably not released from injured primary afferents. With in vivo microdialysis intravenous (i.v.) or intrathecal (i.t.) morphine increased the extracellular level of CCK in the dorsal horn in a naloxone reversible manner. Morphine also released CCK after axotomy, but not during carrageenan-induced inflammation. In contrast, K(+)-stimulation failed to increase extracellular levels of CCK in axotomized rats, but did so in inflamed rats. Double-coloured immunofluorescence technique revealed partial co-localization between CCK-like immunoreactivity (LI) and mu-opioid receptor (MOR)-LI in superficial dorsal horn neurons. The presence of MOR in CCK containing neurons suggests a possible direct influence of opioids on CCK release in the spinal cord. Axotomy, but not inflammation, induced a moderate decrease in CCK- and MOR-LI in the dorsal horn. I.v. morphine further temporarily reduced CCK- and MOR-LIs in axotomized, but not in normal or inflamed, rats. While the effect of morphine on CCK-LI can be interpreted as the result of increased CCK release, the effect on MOR-LI may be related to changes in the microenvironment of the dorsal horn induced by nerve injury.     

Cholecystokinin octapeptide reverses the κ-opioid-receptor-mediated depression of calcium current in rat dorsal root ganglion neurons

Although the cholecystokinin (CCK-8) is reported to antagonize the κ-opioid-receptor-mediated analgesic effect in spinal cord, its mechanism and sites of action remain obscure. In the present study, the whole-cell patch-clamp recording technique was employed to examine the effect of κ-opioid agonist U50488H on voltage-gated calcium channels and the interaction between the CCK-8 and U50488H in acutely isolated rat dorsal root ganglion neurons. The results indicate that the calcium currents elicited in dorsal root antiopioid peptide CCK-8. The effect of the CCK-8 can be abolished by the CCK-B receptor antagonist, L365, 260. While CCK-8 showed a potent opioid-reversal effect, it by itself exerted a slight inhibitory effects on calcium current. This novel observation in the dorsal root ganglion neurons indicates that CCK-8 can antagonize the κ-opioid-receptor-mediated depressant effect on voltage-gated calcium current, and this antagonizing effect appears to be mediated via CCK-B receptor.     

Cholecystokinin Excites Neostriatal Neurons in Rats via CCKA or CCKB Receptors

The effect of iontophoretically applied cholecystokinin (CCK) on neurons of the neostriatum was studied in rats anaesthetized with urethane. The most frequently observed effect of the sulphated octapeptide (CCK-8S) on striatal neurons was excitation. Spontaneously active neurons responded more often to CCK-8S than quiescent cells. Silent, primarily non-responsive neurons could often be stimulated with CCK-8S using glutamate to induce an ongoing discharge. Thus, 45.8% of the 177 neurons studied changed their discharge rate by more than 30%. Certain CCK receptor antagonists could prevent the effect of CCK-8S, fully or at least partly, in the majority of CCK-responsive neurons. The data suggest that cholecystokinin modulates the firing of active neostriatal neurons via the CCKA or the CCKB receptor type. Furthermore, we compared neuronal responses to glutamate with those recorded during concomitant administration of CCK-8S in order to study the interaction of both transmitters, which may be colocalized in striatal afferents. CCK-8S mainly enhanced the excitatory effect of glutamate on striatal neurons, but in several neurons the response to glutamate was reduced. The CCKB receptor antagonist could prevent CCK-8S from increasing the glutamate-induced activation.     

Cholecystokinin antagonists inhibit in vivo voltammetric signals generated by KCl-induced slow wave depolarization in rat caudate

The effect of sulfated cholecystokinin octapeptide (CCK-8S) on the generation of slow wave depolarisation in the rat caudate-putamen (CPu) was studied using in vivo voltammetry. Pressure-ejection of 50 microM CCK-8S into the CPu induced voltammetric signals recorded at widely spaced Nafion-coated carbon fiber microelectrodes. Based on the in vitro selectivity properties of the electrodes, the signals were predominantly due to increases in extracellular concentrations of dopamine (DA). The similar propagation rates of the signals induced by CCK-8S and 100 mM KCl suggests that the CCK-8S-induced signals represent a slow wave depolarization (SWD). Since the CPu was refractory to a second CCK-8S stimulus, the effects of CCK antagonists on DA signals associated with 100 mM KCl-induced SWD were evaluated. Proglumide (4-64 mg/kg) and lorglumide (20-640 micrograms/kg), administered intravenously, decreased KCl-induced DA signals in the CPu in a dose-dependent manner. The antagonistic effect of lorglumide on the KCl-induced signals was partly reversed 130 min after drug administration. The generation of a SWD by CCK-8S and the inhibitory effects of CCK-8S antagonists on KCl-induced signals suggest that the susceptibility of the CPu to KCl-induced SWD may be enhanced by CCK-8S.