中枢外源性胃动素对大鼠脑干胃相关神经元电活动及胃运动的影响

用核团或侧脑室微量注射、微电极细胞外单位放电记录及清醒动物胃运动记录等方法,观察了大鼠下丘脑腹内侧区（ｖｅｎｔｒａｌ ｍｅｄｉａｌ ｈｙｐｏｔｈａｌａｍｕｓ,ＶＭＨ）或侧脑室内（ｉｃｖ）微量注入胃动素（ｍｏｔｉｌｉｎ）对延髓迷走复合体（ｄｏｒｓａｌ ｖａｇａｌ ｃｏｍｐｌｅｘ,ＤＶＣ）神经元电活动和胃运动的影响。结果表明：（１）ＶＭＨ注入胃动素会改变ＤＶＣ胃相关神经元的电活动;（２）ＶＭＨ及侧脑室     

大鼠下丘脑外侧区内微量注射胃动素对胃窦运动和迷走背核复合体神经元电活动的影响

采用清醒大鼠胃运动记录和玻璃微电极记录神经元活动的实验方法 ,研究下丘脑外侧区 (lateralhy pothalamicarea,LHA)微量注射胃动素 (motilin) ,对清醒大鼠胃窦运动和对麻醉大鼠迷走背核复合体 (dorsalvagalcomplex ,DVC)中胃扩张敏感神经元电活动的调节作用。LHA内微量注射胃动素 (0 37nmol/ 0 5 μl)可使胃窦运动增强 76 2 9± 4 0 9% (P <0 0 1)。DVC中 6 0个胃扩张 (gastricdistention ,GD)敏感神经元中 ,39(6 5 % )个GD刺激引起电活动增强 ,2 1(35 % )个电活动减弱 ,分别称之为GD兴奋型神经元和GD抑制型神经元。双侧LHA微量注射胃动素 0 37nmol/ 0 5 μl,14个GD抑制型神经元中有 12个单位放电频率增加 4 4 35± 7 89% (P <0 0 1) ;2 4个GD兴奋型神经元中有 15个单位放电频率减少 7 17± 7 89% (P <0 0 5 )。结果提示 ,中枢胃动素可能通过LHA-DVC-迷走神经实现对胃窦运动的调控     

下丘脑室旁核胃动素对消化功能影响的研究

目的:研究下丘脑室旁核注入胃动素及其拮抗剂对大鼠消化功能和体重增长的研究。方法:将剂量为0.005-5nmol的motilin和GM109注入大鼠下丘脑室旁核,1小时后可观察到大鼠摄食量显著增加并持续到两小时后。进食量的计算是通过预先称量好的鼠粮和应用药物20分钟、1小时、两小时后剩余数量比较而得出。实验持续一周。将实验组和对照组的进食量和体重进行比较。结果:室旁核注入胃动素5nmol的实验组和合并应用GM1090.005nmol的实验组在应用药物后1小时和2小时,可观察到摄食量显著增加(p<0.01),一周后体重也增加(p>0.05),然而摄食量的增加有显著性差异,体重的增加并无显著性差异。其他实验组也没有观察到显著性差异。结论:胃动素有调节消化运动,促进胃肠排空,促进食欲的作用。可能由于胃肠排空是频繁的,没有充裕的时间消化吸收,从而体重增加无显著性差异。     

下丘脑室旁核胃动素对消化功能影响的研究

目的：研究下丘脑室旁核注入胃动素及其拮抗剂对大鼠消化功能和体重增长的研究。方法：将剂量为0.005-5nmol的motilin和GM109注入大鼠下丘脑室旁核,1小时后可观察到大鼠摄食量显著增加并持续到两小时后。进食量的计算是通过预先称量好的鼠粮和应用药物20分钟、1小时、两小时后剩余数量比较而得出。实验持续一周。将实验组和对照组的进食量和体重进行比较。结果：室旁核注入胃动素5nmol的实验组和合并应用GM1090.005nmol的实验组在应用药物后1小时和2小时,可观察到摄食量显著增加（p〈0.01）,一周后体重也增加（p〉0.05）,然而摄食量的增加有显著性差异,体重的增加并无显著性差异。其他实验组也没有观察到显著性差异。结论：胃动素有调节消化运动,促进胃肠排空,促进食欲的作用。可能由于胃肠排空是频繁的,没有充裕的时间消化吸收,从而体重增加无显著性差异。     

Effects of ghrelin on gastric distention sensitive neurons in the arcuate nucleus of hypothalamus and gastric motility in diabetic rats

This study was performed to observe the effects of ghrelin on the activity of gastric distention (GD) sensitive neurons in the arcuate nucleus of hypothalamus (Arc) and on gastric motility in vivo in streptozocin (STZ) induced diabetes mellitus (DM) rats. Electrophysiological results showed that ghrelin could excite GD-excitatory (GD-E) neurons and inhibit GD-inhibitory (GD-I) neurons in the Arc. However, fewer GD-E neurons were excited by ghrelin and the excitatory effect of ghrelin on GD-E neurons was much weaker in DM rats. Gastric motility research in vivo showed that microinjection of ghrelin into the Arc could significantly promote gastric motility and it showed a dose-dependent manner. The effect of ghrelin promoting gastric motility in DM rats was weaker than that in normal rats. The effects induced by ghrelin could be blocked by growth hormone secretagogue receptor (GHSR) antagonist [d-Lys-3]-GHRP-6 or BIM28163. RIA and real-time PCR data showed that the levels of ghrelin in the plasma, stomach and ghrelin mRNA in the Arc increased at first but decreased later and the expression of GHSR-1a mRNA in the Arc maintained a low level in DM rats. The present findings indicate that ghrelin could regulate the activity of GD sensitive neurons and gastric motility via ghrelin receptors in the Arc. The reduced effects of promoting gastric motility induced by ghrelin could be connected with the decreased expression of ghrelin receptors in the Arc in diabetes. Our data provide new experimental evidence for the role of ghrelin in gastric motility disorder in diabetes.     

Ghrelin对糖尿病大鼠下丘脑弓状核胃扩张敏感神经元和胃运动的影响

目的:探讨Ghrelin对糖尿病大鼠下丘脑弓状核胃扩张敏感神经元和胃运动的影响。方法:逆行追踪结合免疫组化观察ARC中GHSR-1的表达,细胞外放电记录,观察ghrelin对GD神经元放电活动的影响及电刺激ARC对GD神经元放电活动和胃运动的影响。结果:电生理实验结果表明,在ARC Ghrelin能够能激发GD兴奋性神经元(GD-E)和GD抑制性神经元(GD-I)。然而,ghrelin可以兴奋更少的GD-E神经元,在正常大鼠中ghrelin对于GD-E的兴奋作用比在DM大鼠中的作用弱。在体胃运动研究表明,在ARC中微量注射ghrelin可以明显的增强胃运动,并且呈现剂量依赖关系。Ghrelin在糖尿病大鼠促胃动力作用低于正常大鼠。Ghrelin诱导的效应可被生长激素促分泌素受体(GHSR)拮抗剂阻断[d-lys-3]-GHRP-6或bim28163。放射免疫法和实时荧光定量PCR数据表明胃血浆ghrelin水平,在ARC ghrelin mRNA的表达水平先上升后下降,糖尿病大鼠(DM)中,在ARC中GHSR-1a mRNA表达保持在一个比较低的水平。结论:ghrelin可以调节GD敏感神经元以及胃运动,通过ARC中ghrelin受体。在糖尿病大鼠中,Ghrelin促进胃运动作用减弱可能与ARC中ghrelin受体表达减少有关。     

Orexin在隔核对大鼠胃传入信息的调控

目的:研究orexin在隔核对大鼠胃传入信息的调控作用。方法:选取健康成年雄性Wistar大鼠138只(体质量250-300 g),记录神经元放电活动,鉴定隔核胃牵张(GD)敏感性神经元;隔核微量注射orexin-A或orexin-A受体拮抗剂SB334867,观察隔核GD敏感性神经元放电活动变化;隔核微量注射不同浓度的orexin-A,观察大鼠胃运动的变化。结果:隔核微量注射orexin-A的大鼠胃运动幅度和频率显著增加,并呈剂量依赖关系(P0.05-0.01),微量注射SB-334867可完全阻断orexin-A对胃运动的影响。隔核微量注射orexin-A后,有36个GD-E神经元兴奋(P0.01),16个GD-I神经元抑制。Orexin-A受体拮抗剂SB334867可完全阻断orexin-A对GD敏感神经元的作用。结论:隔核注射orexin能促进大鼠胃运动,并影响胃牵张敏感神经元的放电活动。     

Effect of motilin on the discharge of rat hippocampal neurons responding to gastric distension and its potential mechanism

The study aims to find the effect of motilin on neuronal activity of gastric distension-responsive neurons in rat hippocampus and its possible mechanism. Single unit discharges in the hippocampal CA1 region were recorded extracellularly by means of four-barrel glass micropipettes in anesthetized rats and the expression of nNOS in hippocampus was observed by fluo-immunohistochemistry staining. Of the 171 recorded neurons, 76.0% were GD-excitatory (GD-E) neurons and 24.0% were GD-inhibited (GD-I) neurons. The 57.6% of GD-E neurons showed an excitatory response to motilin and the same effect was observed in 51.7% GD-I neurons. However, when NOS inhibitor nitro-l-arginine methyl ester (l-NAME) was administrated previously, the followed motilin-induced excitatory responsiveness of GD-responsive neurons was reduced. In contrast, discharge activity of GD-responsive neurons with motilin was enhanced by pretreatment of NO precursor l-arginine. The expression of nNOS-IR positive neurons was significantly increased in CA1 after administration of motilin. Our findings suggested that motilin excited the GD-responsive neurons in the hippocampal CA1 region and the excitatory effect of motilin may be mediated by the endogenous NO.     

胃动素对大鼠下丘脑胃牵张敏感神经元和胃运动的影响(英文)

目的:研究胃动素对下丘脑弓状核胃牵张敏感神经元放电活动和胃运动的影响。方法:采用4管玻璃微电极细胞外记录胃动素对大鼠弓状核胃牵张敏感神经元活动,采用胃内置传感器观察胃动素对对清醒大鼠胃运动的影响。结果:65.5%的弓状核神经元为胃扩张敏感性神经元,其中55.6%为胃扩张兴奋性神经元,44.4%为抑制性神经元。胃扩张刺激后兴奋性神经元的放电频率显著增加(P<0.01),而抑制性神经元的放电频率显著降低(P<0.01)。弓状核内微量注射胃动素,70%的兴奋性神经元在胃扩张刺激后表现为兴奋作用,17.5%的神经元表现为抑制作用,并且放电频率显著增加(P<0.05)。同样,在抑制性神经元中,65.6%在注射胃动素后引起电活动增强,放电频率显著降低(P<0.05)。而胃动素受体拮抗剂GM-109可以完全阻断这种由胃动素诱导的兴奋作用,提示,胃动素在弓状核通过其特异性受体调控神经元活动。在胃运动实验中,弓状核微量注射胃动素后,胃运动的收缩频率和幅度都显著增加(P<0.05);同时,这种兴奋作用也可被GM-109阻断。结论:研究证实了弓状核胃动素神经元接收来自胃感受器的外周躯体感觉传入神经的冲动,并通过某些下级核团通路发挥...     

Hypotensive mechanism of [Leu13]motilin in dogs in vivo and in vitro.

The effects of [Leu13]motilin were examined in vivo after its intravenous administration into anesthetized dogs and in vitro with isolated preparations of canine mesenteric artery. [Leu13]Motilin (0.1-10 nmol x kg(-1), i.v.) induced both strong and clustered phasic contractions in the gastric antrum and duodenum. At doses of over 1 nmol x kg(-1), [Leu13]motilin also produced transient decreases in arterial blood pressure, left ventricular pressure, maximum rate of rise of left ventricular pressure, and total peripheral resistance, and an increase in aortic blood flow and heart rate. A selective motilin antagonist, GM-109 (Phe-cyclo[Lys-Tyr(3-tBu)-betaAla] trifluoroacetate), completely abolished the gastric antrum and duodenal motor responses induced by [Leu13]motilin. In contrast, hypotension induced by [Leu13]motilin (1 nmol x kg(-1)) was unchanged in the presence of GM-109. In isolated mesenteric artery preparations precontracted with U-46619 (10(-7) M), [Leu13]motilin (10(-8)-10(-5) M) induced an endothelium-dependent relaxation, and this was inhibited by a pretreatment with N(omega)-nitro-L-arginine, a competitive inhibitor of NO synthase (10(-4) M). A high dose (10(-4) M) of GM-109 slightly decreased [Leu13]motilin-induced relaxation, and shifted the concentration-response curve of [Leu13]motilin to the right. However, the pA2 value (4.09) of GM-109 for [Leu13]motilin in the present study was conspicuously lower than that previously demonstrated in the rabbit duodenum (7.37). These results suggest that [Leu13]motilin induces hypotension via the endothelial NO-dependent relaxation mechanism and not through the receptor type that causes upper gastrointestinal contractions.     

Interdigestive migrating contractions are coregulated by ghrelin and motilin in conscious dogs

During fasting, gastrointestinal (GI) motility is characterized by cyclical motor contractions. These contractions have been referred to as interdigestive migrating contractions (IMCs). In dogs and humans, IMCs are known to be regulated by motilin. However, in rats and mice, IMCs are regulated by ghrelin. It is not clear how these peptides influence each other in vivo. The aim of the present study was to investigate the relationship between ghrelin and motilin in conscious dogs. Twenty healthy beagles were used in this study. Force transducers were implanted in the stomach, duodenum, and jejunum to monitor GI motility. Subsequent GI motility was recorded and quantified by calculating the motility index. In examination 1, blood samples were collected in the interdigestive state, and levels of plasma ghrelin and motilin were measured. Plasma motilin peaks were observed during every gastric phase III, and plasma ghrelin peaks occurred in nearly every early phase I. Plasma motilin and ghrelin levels increased and decreased cyclically with the interdigestive states. In examination 2, saline or canine ghrelin was administered intravenously during phase II and phase III. After injection of ghrelin, plasma motilin levels were measured. Ghrelin injection during phases II and III inhibited phase III contractions and decreased plasma motilin levels. In examination 3, ghrelin was infused in the presence of the growth hormone secretagogue receptors antagonist [D-Lys3]-GHRP-6. Continuous ghrelin infusion suppressed motilin release, an effect abrogated by the infusion of [D-Lys3]-GHRP-6. Examination 4 was performed to evaluate the plasma ghrelin response to motilin administration. Motilin infusion immediately decreased ghrelin levels. In this study, we demonstrated that motilin and ghrelin cooperatively control the function of gastric IMCs in conscious dogs. Our findings suggest that ghrelin regulates the function and release of motilin and that motilin may also regulate ghrelin.     

下丘脑弓状核微量注射Orexin-A对大鼠胃传入信息和胃运动的影响

目的:探讨ARC orexin-A对胃传入信息以及胃运动的调控及机制。方法:采用细胞外放电记录方法,鉴定ARC orexin胃牵张敏感神经元(Gastric distention sensitive neurons,GD),并探讨ARC内orexin-A对GD神经元放电活动的影响及机制;采用ARC微量注射orexin-A和及其受体阻断剂SB334867,观察大鼠胃收缩幅度和频率的改变。结果:大鼠ARC共记录到149个GD神经元,其中GD-E神经元91个,GD-I神经元58个。ARC微量注射orexin-A,62个(62/91,68.1%)GD-E神经元兴奋性显著增加,其放电频率由4.27±0.58 Hz增加到8.46±0.95 Hz(P0.01);39个(39/58,67.2%)GD-I神经元兴奋性也显著增强,其放电频率由4.02±0.53 Hz增加到5.43±0.57 Hz(P0.05)。然而,ARC给予大鼠orexin-A受体拮抗剂SB334867,再给予orexin-A,orexin-A兴奋效应完全被阻断(P0.05)。胃运动实验结果显示:在ARC注射不同浓度orexin-A,大约5 min后,大鼠胃收缩幅度和频率呈剂量依赖性增加(P0.05~0.01)。ARC注射SB334867,可完全消除orexin-A对大鼠胃运动的兴奋效应(P0.05)。结论:ARC orexin-A对大鼠GD神经元和胃运动有调控作用,该作用可能通过调控Orexin A受体活动实现的。     

下丘脑催产素对大鼠摄食和胃动力的影响及调控研究

目的:探讨下丘脑催产素(OXT)对大鼠摄食和胃动力的影响及调控机制。方法:采用荧光金逆行追踪结合免疫组化实验,观察大鼠视上核(SON)与弓状核(ARC)之间的神经通路;采用核团置管术观察ARC微量注射OXT对大鼠摄食的影响;采用单极电刺激观察电刺激SON对大鼠胃运动的影响及ARC微量注射OXT对大鼠胃运动和胃排空的影响。结果:荧光金逆行追踪结合免疫组化实验显示大鼠SON与ARC之间存在神经通路;ARC微量注射OXT大鼠0-2 h、0-3 h和0-4 h摄食量显著下降,OXT受体拮抗剂阿托西班可完全阻断OXT的抑制摄食作用,注射OXT和缩胆囊素(CCK)受体拮抗剂MK-329混合液后,OXT对大鼠摄食的抑制作用被部分阻断;电刺激SON,大鼠胃运动幅度和频率显著增强,预先向ARC内微量注射阿托西班后再电刺激SON,电刺激SON对胃运动的促进作用进一步增强;ARC微量注射OXT后,大鼠胃运动幅度和频率显著降低,阿托西班可完全阻断OXT对胃运动幅度和频率的抑制作用,MK-329可部分阻断OXT对胃运动幅度和频率的抑制作用;ARC微量注射OTX后,大鼠胃排空率显著降低,阿托西班可完全阻断OXT对胃排空的抑制作用,MK-329可部分阻断OXT对胃排空的抑制作用。结论:SON-ARC内具有OXT神经通路,且该通路由CCK介导。     

Anxiolytic effect of motilin and reversal with GM-109, a motilin antagonist, in mice

There have been few reports on the effects of the brain-gut peptide motilin on the central nervous system (CNS). We administered motilin intracerebroventricularly to mice and investigated the effect of motilin on anxiety using an elevated plus-maze. Motilin produced a significant decrease in anxiety with an inverted U-shaped dose response. To determine whether the anxiolytic effect of motilin was mediated via motilin receptors in the brain, the effect of GM-109, a novel motilin receptor antagonist, was investigated. GM-109 showed a significant and dose-dependent antagonism on the motilin-induced anxiolytic effect. GM-109 administered alone had no effect on anxiety. These results suggest that motilin receptors are present in the brain and may have a role in anxiety and emotion.     

Neural and muscular receptors for motilin in the rabbit colon

Motilin receptors were classically recognized in the gastroduodenal area, where they help to regulate interdigestive motility. More recently, motilin receptors were identified in the colon where their biologic significance remains unclear. We aimed here to characterize the motilin receptors of the rabbit colon. Distal colon and duodenum were obtained from sacrificed rabbits. Tissues homogenized by Polytron were submitted to differential centrifugation to obtain neural synaptosomes or smooth muscle plasma membranes enriched solutions. Motilin binding to these membranes was determined by the displacement of (125)I MOT by the native peptide MOT 1-22, or by peptide analogues MOT 1-12 [CH(2)NH](10-11) or GM-109 and by erythromycin derivative GM-611. Motilin binding capacity was maximum in colon nerves (49.5 +/- 6.5 fmol/mg protein vs. 19.9 +/- 2.5 in colon muscles or 9.4 +/- 2.8 and 6.6 +/- 1.2 in duodenal muscles and antral nerves respectively); all tissues expressed similar affinity for MOT 1-22, and the motilin agonist GM-611 bound equally to neural or muscle tissues from the rabbit colon; the synthetic antagonist MOT 1-12 [CH(2)NH](10-11) showed greater affinity for colon nerves than for colon muscles (plC50: 7.23 +/- 0.07 vs. 6.75 +/- 0.03). Similar results were obtained with the peptide antagonist GM-109; receptor affinity toward MOT 1-12 [CH(2)NH(10-11)] was always five times superior in neural tissues, whether they came from the colon or the antrum, than in muscle tissues, whether they were obtained from colon or from duodenum. Motilin receptors are found in very high concentration in nerves and in muscles from rabbit colon; specific motilin receptor subtypes are identified in nerves (N) and muscles (M) of the rabbit colon; N and M receptor subtypes seem independent of the organ location.     

Possible mechanisms of amygdala participation in the regulation of gastric motor activity

Mechanisms of the amygdala central nucleus (CNA) influence on gastric motor reflex activity were studied in electrophysiological and neuroanatomical experiments in Wistar rats. In the anaesthetized animals, electrical stimulation of the CNA affected spontaneous gastric motility and caused inhibitory as well as excitatory changes of vagus-induced gastric relaxation. The most significant and mainly inhibitory effects were observed under the stimulation of the medial CNA. Microinjection of the anterograde tracer Phaseolus vulgaris-leucoagglutimn (PHA-L) into the different divisions of the CNA revealed direct projections from its dorso-medial portion to the gastric related area of the dorsal vagal complex. Electrical stimulation of this amygdaloid area was found to change activity of the bulbar gastric related neurons. Inhibitory and excitatory changes of their vagus-induced responses under the amigdala stimulation were manifested as a general modulation of all phases of the reaction or a selective modulation of some of them. These mechanisms may underlie the amygdalo-fugal modulation of gastric motor reflex activity.     

Endogenous CCK is not involved in the regulation of interdigestive gastrointestinal and gallbladder motility in conscious dogs.

In this study, we assessed whether endogenous CCK is involved in the regulation of interdigestive gastrointestinal and gallbladder motility in conscious dogs with force transducers chronically implanted in the gastric antrum, duodenum, jejunum and gallbladder. L364718 at a dose of 1.0 mg/kg was used as a specific and potent CCK receptor blocker, and its effect on spontaneous interdigestive motility and plasma motilin release were examined. Additionally, the contractile activity of exogenous synthetic canine motilin (20-100 ng/kg) with or without pretreatment with L364718 at a dose of 1.0 mg/kg was assessed. Whether the blocking effect of L364718 on CCK receptors was sufficient or not was verified by giving CCK-OP at a bolus dose of 10 ng/kg. As a result, cyclic changes in interdigestive motor activity and the plasma motilin concentration were not affected by pretreatment with L364718. L364718 also did not affect motilin-induced interdigestive contractile activity in the gastrointestinal tract and gallbladder. On the other hand, the effect of CCK-OP was completely abolished by pretreatment with L364718. It is concluded that endogenous CCK is not involved in the regulation of spontaneous and motilin-induced interdigestive contractions in the canine gastrointestinal tract and gallbladder.     

生长素对胃运动和对海马胃肠敏感神经元放电活动的影响

目的:探讨海马ghrelin对GD敏感神经元放电和弓状核ghrelin对胃运动的影响。方法:在细胞外记录海马的放电情况,并且检测清醒大鼠的胃运动。通过PCR免疫印迹和免疫荧光组织化学染色等方法来测定GHSR-1a在海马中的表达。用逆行追踪和免疫荧光组织化学染色检测ghrelin神经元的投射情况。Ghrelin况荧光金双标记的神经元以及GHSR-1a的表达分别可以在ARC和海马中观察到。结果:Ghrelin或者ARC电刺激可以兴奋海马区的胃牵张敏感神经元。Ghrelin受体拮抗剂[d-Lys-3]-GHRP-6预处理可以完全或者部分阻断这种兴奋作用。海马注射ghrelin可以显著促进胃运动,并且呈现剂量依赖关系,而且这种作用可以被[d-Lys-3]-GHRP-6所阻断。电刺激ARC能够促进胃运动。然而,预处理时[d-Lys-3]-GHRP-6可以减弱这些作用。电损毁海马可以减弱胃运动的兴奋作用,这个作用通过电刺激ARC产生的。结论:通过海马促进胃运动中ghrelin起着重要的作用。ARC可能参与调节海马对胃动力的影响。     

下丘脑弓状核PYY对大鼠摄食、胃运动和能量代谢的影响及机制

目的:探究YY肽(PYY)对雄性Wistar大鼠的摄食、胃运动和能量代谢的影响及潜在机制。方法:采用免疫组织化学实验方法观察大鼠下丘脑弓状核(ARC)中Y2受体的表达;通过ARC微量注射PYY,观察其对下丘脑中编码摄食相关代谢激素的m RNA表达以及ARC中PYY反应性神经元的放电频率、食物摄入量及水摄入量、氧气消耗(VO_2)、CO_2产生(VCO_2)及能量代谢的影响。结果:免疫组化结果显示大鼠ARC内存在Y2受体;大鼠ARC注射PYY能够兴奋PYY反应性神经元,上调可卡因-苯丙胺调节转录肽(CART)及促肾上腺皮质释放激素(CRH)等抑食肽m RNA的表达,下调神经肽Y(NPY)及下丘脑泌素(HCRT)等促食肽m RNA的表达;且抑制大鼠食物摄入量,并参与调控大鼠呼吸、能量代谢及胃运动的改变。结论:ARC微量注射PYY可减少食物摄入并调节全身能量平衡,PYY可能是一种新型代谢肽。     

Coordination of motilin and ghrelin regulates the migrating motor complex of gastrointestinal motility in Suncus murinus

Motilin and ghrelin are the gastrointestinal (GI) hormones released in a fasting state to stimulate the GI motility of the migrating motor complex (MMC). We focused on coordination of the ghrelin/motilin family in gastric contraction in vivo and in vitro using the house musk shrew (Suncus murinus), a ghrelin- and motilin-producing mammal. To measure the contractile activity of the stomach in vivo, we recorded GI contractions either in the free-moving conscious or anesthetized S. murinus and examined the effects of administration of motilin and/or ghrelin on spontaneous MMC in the fasting state. In the in vitro study, we also studied the coordinative effect of these hormones on the isolated stomach using an organ bath. In the fasting state, phase I, II, and III contractions were clearly recorded in the gastric body (as observed in humans and dogs). Intravenous infusion of ghrelin stimulated gastric contraction in the latter half of phase I and in the phase II in a dose-dependent manner. Continuous intravenous infusion of ghrelin antagonist (d-Lys3-GHRP6) significantly suppressed spontaneous phase II contractions and prolonged the time of occurrence of the peak of phase III contractions. However, intravenous infusion of motilin antagonist (MA-2029) did not inhibit phase II contractions but delayed the occurrence of phase III contractions of the MMC. In the in vitro study, even though a high dose of ghrelin did not stimulate contraction of stomach preparations, ghrelin administration (10(-10)-10(-7) M) with pretreatment of a low dose of motilin (10(-10) M) induced gastric contraction in a dose-dependent manner. Pretreatment with 10(-8) M ghrelin enhanced motilin-stimulated gastric contractions by 10 times. The interrelation of these peptides was also demonstrated in the anesthetized S. murinus. The results suggest that ghrelin is important for the phase II contraction and that coordination of motilin and ghrelin are necessary to initiate phase III contraction of the MMC.