缩胆囊表和促胰液表对豚鼠离体胃平滑肌运动的影响

用８个肌槽同时记录豚鼠胃不同部位肌条的收缩活动,以观察八肽缩胆囊素（ＣＣＬ－８）和促胰液素的影响。结果表明,ＣＣＫ－８能（１）增高各部位纵行肌和环行肌的张力;（２）加快胃体纵行肌,胃窦纵行肌、环行肌和幽门环行肌的收缩频率;（３）增大胃窦环行肌收缩波平均振幅和（４）增加幽门环行肌收缩波运动指数,但减少胃全和胃窦纵行肌收缩波平均振幅。上述作用均不能被阿托口 和炎痛所阻断。而促胰液素对各部位肌条的收缩活     

促胰液素和胆囊收缩对狗胃肌条活动的影响

促胰液素和胆囊收缩对狗胃肌条活动的影响郑天珍李伟瞿颂义张英福邱小青（兰州医学院生理学教研室,兰州７３００００）促胰液素和胆囊收缩素（ＣＣＫ－８）对胃运动具有重要的调节作用,但研究报道的结果常不一致。故我们取狗离体胃各部位的平滑肌肌条,观察对这两种激素...     

八肽胆囊收缩素对吗啡抑制大鼠离体空肠电与收缩活动的对抗作用

本研究探讨了八肽胆囊收缩素（ＣＣＫ－８）对抗吗啡对大鼠离体空肠电与收缩活动的作用。结果表明,吗啡能抑制ＡＣｈ对空肠峰波发放和收缩的加强作用;ＣＣＫ－８可对抗吗啡的作用;在此基础上,ＣＣＫ－Ａ受体拮抗剂ｄｅｖａｚｅｐｉｄｅ（１０ｎｍｏｌ／Ｌ）能完全翻转ＣＣＫ－８的抗吗啡作用,但是ＣＣＫ－Ｂ受体拮抗剂Ｌ－３６５,２６０在１０ｎｍｏｌ／Ｌ时可部分翻转、在３０ｎｍｏｌ／Ｌ时能完全翻转ＣＣＫ－８的作用。上述     

氢溴酸槟榔碱对豚鼠离体胃窦环行肌条收缩活动的影响

目的：观察氢溴酸槟榔碱对豚鼠离体胃窦环行肌条的收缩活动并探讨其作用机理。方法：将胃窦环行肌条置于灌流肌槽内,采用累积加氢溴酸槟榔碱和分别加阻断剂的方法,观察对肌条的收缩活动的影响。结果：10^-7mol/L、10^-6mol/L浓度的槟榔碱对胃窦环行肌条的收缩波平均振幅有增大作用;10^-6mol/L浓度槟榔碱增高环行肌条的张力,4-DAMP可阻断槟榔碱增加胃窦环行肌条的收缩活动的作用,加拉明未阻断槟榔碱兴奋胃窦环行肌条的作用。结论：氢溴酸槟榔碱可兴奋豚鼠胃窦环行肌条的收缩活动,该作用经由胆碱能M3受体,而不是胆碱能M2受体的途径。     

促胰液素对血管灌流大鼠离体胃运动的抑制作用

本工作采用血管灌流大鼠离体胃制备,探讨促胰液素对胃运动的影响。结果表明:(1)促胰液素能明显抑制胃窦自发和五肽胃泌素兴奋的胃运动;(2)抗促胰液素血清可完全取消促胰液素的抑制胃窦运动作用;(3)抗生长抑素血清和消炎痛都能阻断促胰液素的抑制胃窦运动作用。上述结果提示,促胰液素的抑制作用除通过直接作用于促胰液素受体外,还可能部分通过胃窦局部生长抑素和前列腺素介导来抑制胃的运动。     

八肽胆囊收缩素减轻肿瘤坏死因子诱导的离体兔肺动脉反应性变化及内皮细胞损伤

为探讨八肽胆囊收缩素（ＣＣＫ－８）缓解内毒素休克时肺动脉高压的作用机制,应用离体血管环张力测定技术及扫描电镜方法,观察了ＣＣＫ－８对肿瘤坏死因子α（ＴＮＦ－α）引起的肺动脉反应性及肺动脉内皮细胞超微结构变化的影响。结果显示：离体脑动脉经ＴＮＦ－α（４０００Ｕ／ｍｌ）孵育２ｈ对苯肾上腺素（ＰＥ）的收缩反应、对乙酰胆碱（ＡＣｈ）及硝普钠（ＳＮＰ）的内皮依赖性及非内皮依赖性舒张反应均无明显影响。ＴＮＦ－     

栀子对兔胃平滑肌体外运动的影响

目的：观察利胆药物-栀子对兔离体胃平滑肌的影响,并初步探讨其作用机制。方法：取兔胃肌条,安置在各恒温灌流肌槽中并用BL-310生物技能实验系统记录胃各部平滑肌条的收缩活动,结果：栀子显著升高兔胃底和胃体纵行肌条张力,增加其收缩频率,减小胃体收缩波平均振幅,并有剂量依赖关系。结论：栀子对胃肌条收缩活动具有明显的兴奋作用,这种兴奋作用部分经由M受体介导。     

杏仁核内注射CCK—8抑制胃运动的机制

应用脑核团内微量注射和核团电刺激方法,观察杏仁基底内侧（ＢＭＡ）对胃运动的影响,分析ＢＭＡ与下丘脑腹内侧核（ＶＭＨ）的机能联系。结果如下：（１）双侧ＢＭＡ内注射八肽胆囊收缩素（ＣＣＫ－８）（５０ｎｇ／ｌμｌ）,出现胃内压（ＩＧＰ）和胃运动频率（ＧＭＦ）显著下降（Ｐ〈０．０１）。（２）ＢＭＡ内注射ＣＣＫ－Ａ受体阻断剂［Ｌ３６４,７１８］（１００ｎｇ／ｌμｌ）或ＣＣＫ－Ｂ受体阻断剂［Ｌ３６５,２６０］     

胆囊收缩素对IL－1β损伤的胰岛β细胞功能的保护作用及其机制分析

本实验在分离培养的新生大鼠胰岛上,观察了胆囊收缩素（ＣＣＫ－８）对白细胞介素－１β（ＩＬ—１β）损伤的胰岛β细胞功能的影响。并就其机制进行初步分析。结果表明：（１）ＩＬ—１β（５,１０,２０Ｕ／ｍｌ）能抑制葡萄糖（２０ｍｍｏｌ／Ｌ）刺激的胰岛素分泌,其抑制作用具有量效关系,抑制率分别为５３．４％,６０．５％和７０．７％。（２）ＣＣＫ－８对ＩＬ－１损伤的胰岛β细胞的功能具有保护作用。预防性地给予ＣＣＫ－８（１０￣（－１０）,１０￣（－９）,１０￣（－８）,１０￣（－７）ｍｏｌ／Ｌ）能防止ＩＬ－１β对葡萄糖刺激的胰岛素分泌的抑制作用。治疗性地给予ＣＣＫ－８也能恢复胰岛对葡萄糖刺激的胰岛素分泌的能力。（３）ＣＣＫ　Ａ型受体阻断剂Ｌ３６４７１８（１０ｎｍｏｌ／Ｌ）能阻断ＣＣＫ－８的保护作用,表明这一作用可能是通过ＣＣＫ受体实现的。（４）ＩＬ－１β抑制胰岛素分泌的同时,能升高胰岛组织内ｃＧＭＰ水平,而ＣＣＫ－８能阻止ＩＬ－１引起的ｃＧＭＰ水平的升高。     

胃扩张刺激对大鼠大脑皮层及海马CCK mRNA表达的影响

胆囊收缩素（ｃｈｏｌｅｃｙｓｔｏｋｉｎｉｎ,ＣＣＫ）是脑肠肽中的一种,被认为是饱因子。本实验采用以地高辛标记的ＣＣＫ ｃＤＮＡ为探针的原位杂交和半定量ＲＴ－ＰＣＲ技术。用水囊扩张胃作为对胃壁的机械刺激模拟食物对胃的充盈作用,观察大鼠大脑皮层和海马内含ＣＣＫ神经元ＣＣＫ ｍＲＮＡ表达的变化情况。     

Effects of cholecystokinin-8 induced gastric dysmotility on bile regurgitation during stress and molecular mechanisms

OBJECTIVE: To illustrate the existence of bile regurgitation under stress condition, and explore the possible effects and related mechanism of changes of plasma cholecystokinin octapeptide (CCK-8) and intragastric pH on stress-induced bile regurgitation in rats. METHODS: (1) Changes in plasma CCK-8 and gastric bile concentration were respectively measured by using radioimmunoassay (RIA) method while simultaneously calculating gastric ulcer index (UI) and intragastric pH; (2) Each isolated gastric strips were suspended in a tissue chamber to record the contractile responses by polyphysiograph; (3) The responsiveness of gastric smooth muscle cells (SMCs) to sulfated cholecystokinin octapeptide (CCK-8S) were examined using fura-2-loaded microfluorimetric measurement of intracellular calcium concentration ([Ca(2+)]i); (4) The current of L-type calcium channels (I(CaL)) of SMCs were recorded by patch clamp techniques. RESULTS: (1) Compared with the normal control group, plasma CCK-8 and gastric bile concentration significantly increased during stress (p<0.01) and both simultaneously reached the peak at the time point of 2 h after stress; UI and intragastric pH apparently increased (p<0.01); (2) Significant changes to CCK-8S were found in the mean contractile amplitude and frequency of circular muscle (CM) and longitudinal muscle (LM) of gastric antrum and pylorus; (3) CCK-8S-evoked significant increase in [Ca(2+)]i (p<0.01) could be suppressed by CCK-A receptor (CCK-AR) antagonist; whereas a small but significant increase was still elicited by CCK-8S under condition of the removal of extracellular calcium or by given nifidipine; (4) CCK-8S-intensified calcium current (I(CaL)) apparently inhibited by respective administration of nifidipine, Ca(2+)-ATPase inhibitors or calcium dependent chloride channel (I(Cl-Ca)) blocker (p<0.01). CONCLUSION: Gastric mucosal damage induced by bile regurgitation is closely connected with gastric antrum and pylorus dysmotility evoked by CCK-8 during the stress. CCK-8S-evoked [Ca(2+)]i increase in gastric antrum and pylorus SMC depends on the release of intracellular calcium stores which activates L-type voltage-dependent calcium channels (VDCC) through the activation of calcium dependent chloride channels.     

Pharmacological examination of cholecystokinin (CCK-8)-induced contractile activity in the rat isolated pylorus

The actions of cholecystokinin (CCK) in the production of a satiety-like state have been suggested to be mediated via receptors for CCK which are located in the pylorus. We investigated the actions of CCK and other pharmacological agents upon the isolated rat pylorus in vitro. We used the change in isometric tension of the tissue preparation (contraction amplitude) as the measure of the effects of the pharmacological agents. Cholecystokinin COOH-terminal octapeptide (CCK-8) was observed to elicit contraction in a dose-dependent manner, with the half-maximal dose (ED50) in the vicinity of 1 nM. Rapid desensitization to CCK was observed. The contraction amplitude was atropine-independent, and was not significantly antagonized by a wide variety of other pharmacological agents. The Na+-channel blocker tetrodotoxin was without effect upon contractile amplitude, as was the K+-channel blocker 4-aminopyridine, except at very high concentrations. Neurotensin, bombesin, and the substance P and bombesin antagonist spantide all elicited contraction in the isolated tissue; neurotensin had a similar potency to CCK-8 and bombesin was 10-15-fold less potent than CCK-8. Unsulfated CCK-8 was at least 170-fold less potent than sulfated CCK-8 and tetragastrin was at least 500-fold less potent than CCK-8. These results suggest that pyloric CCK receptors, which appear to have a pharmacological profile typical of peripheral CCK receptors, may have a physiological role in the peptidergic control of gastric emptying in the rat.     

Coordinated gastric and sphincter motility evoked by intravenous CCK-8 as monitored by ultrasonomicrometry in rats

Gastric and sphincter motility evoked by intravenous injection of CCK-8 were investigated in urethane-anesthetized rats. Digital ultrasonomicrometry was used to monitor pyloric (PYL), antral (ANT), corpus (COR), and lower esophageal sphincter (LES) movements while simultaneously measuring intragastric pressure (IGP) and, in some experiments, subdiaphragmatic intraesophageal pressure (sIEP). Intracrystal distances (ICD) were measured continuously between pairs of piezoelectric crystals affixed to the serosa of PYL, ANT, COR (circular and longitudinal), and LES. Consecutive intravenous injections of CCK-8 (0.3, 1, and 3 microg/kg) at 30-min intervals caused dose-dependent simultaneous tonic contractions of PYL and ANT, LES opening, and drops in IGP with peak changes at 3 microg/kg of -17.9 +/- 2.1, -7.7 +/- 2.5, 6.5 +/- 1.4, and -29.2 +/- 3.8%, respectively, whereas intravenous saline had no effect. Rhythmic contractile activity was inhibited by CCK-8. COR responses were not significantly different from vehicle controls for most metrics, and the direction of response for circular COR varied between preparations, although not for repeated trials in a single preparation. During the LES response to CCK-8, sIEP rose in parallel with drops in IGP, indicating formation of a common cavity. Recovery of LES ICD after intravenous CCK occurred more rapidly than recovery of PYL ICD, suggesting the importance of preventing simultaneous patency of gastroesophageal and gastroduodenal passages. The CCK(A) receptor antagonist devazepide (500 microg/kg intravenous) inhibited motion responses evoked by intravenous CCK-8. These data revealed CCK-8-induced gastric and sphincter activity consistent with retropulsion of gastric content.     

胃动素对大鼠胃平滑肌细胞收缩活动的作用

本研究用大鼠游离的胃平滑肌细胞,观察胃动素对胃平滑肌细胞的收缩作用。结果表明：（１）胃动素明显增强单个胃平滑肌细胞收缩活动,在生理剂量１０（－１１）─１０（－１０）ｍｏｌ范围内,呈剂量依赖性。（２）不同胃分区平滑肌细胞对冒动素兴奋反应不同,胃动素对胃窦平滑肌细胞收缩强度大于胃体和幽门。（３）给予抗胃动素血清可以完全取消胃动素对胃肌细胞的收缩反应,而阿托品、ＴＴＸ、甲氰米胍、ｌｏｘｉｇｌｕｍｉｄｅ均不影响胃动素的作用。（４）给予胞内钙释放阻断剂ＴＭＢ－８可抑制胃动素对目肌细胞的收缩作用。上述结果提示,胃动素对胃平滑肌细胞的直接作用是由胃动素受体所介导,且与胞内Ｃａ（２＋）释放起重要作用。     

In vitro response of rat gastrointestinal segments to cholecystokinin and bombesin

In previous studies of the rat gastrointestinal (GI) tract, we have demonstrated specific binding of cholecystokinin (CCK) to the pylorus and of bombesin (BN) to the gastric fundus, gastric antrum, duodenum, and ileum. We now present the results of an investigation of the in vitro response of the same regions of the rat GI tract to CCK-8 (the active octapeptide of CCK) and BN. Sections of rat fundus, antrum, pylorus, duodenum, and ileum were suspended in a Tyrode buffer and attached to an isometric pressure transducer in a longitudinal orientation. Dose-response curves to CCK-8 and BN were generated for each tissue. CCK-8 consistently induced a change only in pylorus, while BN induced a response from fundus, antrum and duodenum. With the exception of the lack of ileal response to BN, the regions of the rat GI tract which biologically respond (i.e., contract or relax) to CCK-8 or BN were the same regions in which we have located BN and CCK-8 binding sites. This correlation supports the hypothesis that GI function is modified by specified hormone-receptor interactions with these peptides.     

Regional gastric contractility alterations in a diabetic gastroparesis mouse model: effects of cholinergic and serotoninergic stimulation

The C57BLKS/J db/db mouse develops hyperglycemia and has delayed gastric emptying that is improved with tegaserod, a partial 5-HT4 agonist. Our aims here were to determine regional gastric contractility alterations in C57BLKS/J db/db mice and to determine the effects of serotonin and tegaserod. The contractile effects of bethanechol, serotonin, and tegaserod in fundic, antral, and pyloric circular muscle were compared in C57BLKS/J db/db mice and normal littermates. The effects of tetrodotoxin, atropine, and 5-HT receptor antagonists were studied. Contractions in response to bethanechol were decreased in the fundus, similar in the antrum, but increased in the pylorus in diabetic mice compared with controls. Serotonin and, to a lesser extent, tegaserod caused contractions that were more pronounced in the fundus than in the antrum and pylorus in both diabetic and normal mice. Serotonin-induced contractions were partially inhibited by atropine, the 5-HT4 antagonist GR113808, and the 5-HT2 antagonist cinanseron but not tetrodotoxin. Regional gastric contractility alterations are present in this diabetic gastroparesis mouse model. Fundic contractility was decreased, but pyloric contractility was increased in the pylorus to cholinergic stimulation in diabetic mice. Serotonin's contractile effect is mediated, in part, through muscarinic, 5-HT2, and 5-HT4 receptors. This study suggests that fundic hypomotility and pyloric hypercontractility, rather than antral hypomotility, play important roles for the gastric dysmotility that occurs in diabetes.     

Contractile effects of 16-methyl analogues of PGE2 on the circular and longitudinal muscles of the guinea-pig isolated colon.

The mechanical effects of 16-methyl analogues of PGE2, mainly 16,16-dimethyl PGE2, on circular and longitudinal muscles of the guinea-pig isolated proximal colon were investigated. In circular muscle strips, PGE2 100 nM produced an initial contraction followed by relaxation, while 16(R)-methyl PGE2 and 16,16-dimethyl PGE2 (1 nM - 1 microM) produced sustained contractions. In longitudinal muscle strips, PGE2 and 16-methyl analogues of PGE2 produced only contractions. The contractile responses of both muscle strips to 16,16-dimethyl PGE2 were not influenced by atropine or tetrodotoxin, indicating that these analogues act directly on the muscles, but were eliminated by the omission of extracellular Ca ions or in the presence of 1 mM lanthanum ions. However, verapamil, a Ca channel blocker, did not block the contractile response to the methyl analogues in circular muscle strips, although it completely inhibited the contractile response of longitudinal muscle strips. These results suggest that the contractile effect of 16-methyl analogues of PGE2 on the circular muscle may be due to an increased influx of Ca ions mainly via receptor-sensitive and partly voltage-sensitive Ca channels, while the contractile effect of the analogues on the longitudinal muscle may be due to an increase in influx of Ca ions via voltage-sensitive Ca channels.     

Bombesin-induced changes in membrane potential-dependent phasic contractions of cat gastric muscle

Electrical and contractile activities of smooth muscle strips isolated from the circular muscle layer of cat gastric antrum were studied using the sucrose gap technique. Bombesin (10(-8) mol/l) depolarized the gastric muscle; this was accompanied by an increase in the strip tone, in the plateau action potential frequency and in both the frequency and the amplitude of the spike potentials as well as by a shortening of the plateau action potential duration. Both the frequency and the amplitude of the phasic contractions increased thereafter. The changes in the frequency of the plateau action potentials and contractions were not influenced either by antagonists of cholinergic and adrenergic receptors or by TTX. In the presence of the Ca antagonists D600 (10(-6) mol/l) and nifedipine (10(-7) mol/l) or in Ca-free medium containing EGTA the effect of bombesin on the frequency of the plateau action potentials and phasic contractions remained unchanged; however, spike potentials were not observed and no increase in the amplitude of phasic contractions occurred. UV-light inactivation of nifedipine restored the typical bombesin effect on the electrical and contractile activities of the gastric smooth muscle. The present data suggest that the effect of bombesin on the frequency of both plateau action potentials and phasic contractions is not linked with Ca2+ influx.     

Relative contributions of "pressure pump" and "peristaltic pump" to gastric emptying

The relative contributions to gastric emptying from common cavity antroduodenal pressure difference ("pressure pump") vs. propagating high-pressure waves in the distal antrum ("peristaltic pump") were analyzed in humans by high-resolution manometry concurrently with time-resolved three-dimensional magnetic resonance imaging during intraduodenal nutrient infusion at 2 kcal/min. Gastric volume, space-time pressure, and contraction wave histories in the antropyloroduodenal region were measured in seven healthy subjects. The subjects fell into two distinct groups with an order of magnitude difference in levels of antral pressure activity. However, there was no significant difference in average rate of gastric emptying between the two groups. Antral pressure history was separated into "propagating high-pressure events" (HPE), "nonpropagating HPEs," and "quiescent periods." Quiescent periods dominated, and average pressure during quiescent periods remained unchanged with decreasing gastric volume, suggesting that common cavity pressure levels were maintained by increasing wall muscle tone with decreasing volume. When propagating HPEs moved to within 2-3 cm of the pylorus, pyloric resistance was found statistically to increase with decreasing distance between peristaltic waves and the pylorus. We conclude that transpyloric flow tends to be blocked when antral contraction waves are within a "zone of influence" proximal to the pylorus, suggesting physiological coordination between pyloric and antral contractile activity. We further conclude that gastric emptying of nutrient liquids is primarily through the "pressure pump" mechanism controlled by pyloric opening during periods of relative quiescence in antral contractile wave activity.     

Endogenous prostaglandins regulate spontaneous contractile activity of uterine strips isolated from non-pregnant pigs

Myometrial strips isolated from non-pregnant pigs show spontaneous contractile activity. In the present study, the involvement of endogenous prostaglandins in regulation of uterine spontaneous contraction was investigated using mechanical, immunohistochemical and biochemical approaches. Immunohistochemical study and Western blot analysis for immunoreactive cyclooxygenase (COX) indicated that COX-1 but not COX-2 was expressed predominantly in the myometrium of non-pregnant pigs in a muscle layer-dependent manner (longitudinal muscle>circular muscle). Pretreatment of uterine strips with indomethacin and selective COX-1 inhibitors (SC-560 and FR122047) significantly reduced both the amplitude and frequency of spontaneous contraction in the longitudinal muscle, but inhibition by COX inhibitors was negligible in the circular muscle. On the other hand, CAY10404, a COX-2 inhibitor, did not change the spontaneous contraction in either of the muscle layers. Pretreatment with SC-560 reduced myometrial PGF(2alpha) and PGE(2) levels. Contractile FP and EP(3) receptors were expressed in a muscle layer-dependent manner (longitudinal muscle>circular muscle), similar to the expression pattern of COX-1. In conclusion, endogenous prostaglandins produced by COX-1 regulate spontaneous contractile activity of non-pregnant porcine uterine longitudinal muscle selectively due to the heterogeneous expression of contractile prostanoid receptors and COX-1.