MN9202降压作用的实验研究

目的 :探讨 2 ,6 -二甲基 - 4- （3-硝基苯基 ） - 1,4-二氢 - 3,5 -吡啶二羧酸 - 3-甲酯 - 5 -正戊酯 （MN92 0 2 ）的降压作用及其机制。方法 :应用清醒大鼠及肾性高血压大鼠 ,观察 MN92 0 2的降压作用 ,并采用离体兔胸主动脉张力实验观察 MN92 0 2的扩血管作用。结果 :腹腔注射 MN92 0 2 10 ,30 ,10 0 μg/ kg对正常动物和肾性高血压大鼠均可产生明显的降压作用 ,具有明显的剂量依赖关系。MN92 0 2和 Nitrendipine对抗 KCl引起家兔主动脉收缩的 IC50 分别为2 .1μmol/ L 和 3.1μmol/ L,Emax则为 6 8.8%和 5 4.9%;对抗 NE引起收缩的 IC50 分别是 2 .0 μm ol/ L 和 2 .2 μmol/L ,Emax是 34 .6 %和 32 .2 %;其作用不受内皮的影响 ;MN 92 0 2可显著抑制 NE的依赖细胞外 Ca2 +收缩反应 ,而对内 Ca2 +收缩反应则无明显抑制作用。结论 :MN92 0 2具有明显的扩血管效应 ,其作用与其抑制电压依赖性钙通道 ,减少 Ca2 +内流有关。     

MN9202对离体大鼠胸主动脉的舒张作用及其机制

目的 :研究新合成的二氢吡啶类钙拮抗剂 2 ,6 二甲基 4 （3 硝基苯基 ） 1,4 二氢 3,5 吡啶二羧酸 3 甲酯 5 正戊酯 （MN92 0 2 ）对离体大鼠胸主动脉的舒张作用及其机制。方法 :采用离体血管灌流的方法 ,观察MN92 0 2对内皮完整和去内皮胸主动脉的舒张作用 ,以及TEA（四乙铵 ）对这一过程的影响。结果 :MN92 0 2可引起剂量依赖性的舒张血管效应且无内皮依赖性 ;钙激活钾通道 （KCa）的阻断剂TEA（10 -5mol/L）可减弱 （但不完全阻断 ）MN92 0 2舒张血管的作用 ,使量效曲线右移。结论 :MN92 0 2对胸主动脉具有不依赖内皮的舒张作用 ,此作用是通过阻断L 型钙通道的钙内流 ,本研究也证明MN92 0 2舒张胸主动脉作用可能还与KCa有关。     

川穹嗪对维拉帕米致急性左心衰竭家兔心功能的影响

目的:观察不同剂量的川穹嗪对维拉帕米致急性左心衰(AHF)家兔心功能的影响。方法: 采用静脉滴注维拉帕米的方法,建立家兔AHF模型。静脉注射不同剂量的川穹嗪观察其对AHF家兔心脏血流动力学的影响。结果: 小剂量（8.0 mg/kg）、大剂量（16.0 mg/kg）的川穹嗪均能明显改善AHF家兔的多项血流动力学指标,明显增高AHF家兔的收缩压（SBP）、舒张压（DBP）、脉压（PP）、左室收缩压（LVSP）、左室内压最大上升速度（+dp/dtmax）以及左室内压最大下降速度（-dp/dtmax）（n=5,P<0.05）,明显降低AHF家兔的左室舒张末压（LVEDP）（n=5,P<0.05）。川穹嗪扩张血管的作用呈浓度依赖性,但其增强心衰心肌收缩力的作用小剂量与大剂量无明显差异。结论: 川穹嗪可显著改善AHF家兔的血流动力学参数,有助于AHF的治疗。     

食管超声多普勒监测腹腔镜胆囊切除术血流动力学的变化

目的 :应用经食管超声多普勒血流动力学监测仪 ,观察腹腔镜胆囊切除术 （laparoscopic cholecystectomy,L C）期间的血流动力学的变化。方法 :ASA ～ 级择期行 L C患者 12例为研究对象。麻醉诱导插管后将Hemosonic TM 10 0血流动力学监测仪超声探头经口放入食管 ,探头置于第三四肋骨间隙 （或第五六胸椎间隙 ）持续监测心排出量 （CO）、每搏量 （SV）、心指数 （CI）、血流峰速度 （PV）、血流加速度 （Acc）和左室射血时间指数 （L VETI） ,每隔 5m in输入平均动脉压 （MAP）值后计算体循环血管阻力 （SVR）值。麻醉平稳和各项监测完成后 ,于气腹前测定基础值 ,然后于气腹即刻、气腹后 10、2 0和 3 0 min及放气后 5min作重复测定。手术期间维持气腹压力 2 k Pa。结果 :研究过程中 ,Sp O2 和 PETCO2 维持在正常值范围并保持稳定 ,ECG未见心律失常。麻醉后气腹前 ,血流动力学各指标维持在正常值范围。气腹后 CO,SV,CI,PV,Acc和 L VETI无显著变化 ,而 MAP和 SVR均显著增加（P<0 .0 5） ,但仍属正常范围。结论 :ASA I～ II级患者行腹腔镜手术是安全的 ,术中血流动力学基本稳定     

硝酸甘油治疗充血性心力衰竭的剂量探讨

采用静滴叠加剂量硝酸甘油（ＮＴＧ）治疗充血性心力衰竭（ＣＨＦ）２４例，观察其与血流动力学急性效应的变量关系。结果显示：ＮＴＧ１２０～１４０μｇ／ｍｉｎ时肺毛楔压和体循环阻力均明显下降，且心排血量显著增加，认为，此剂量为治疗ＣＨＦ的理想剂量。     

哌唑嗪对慢性充血性心力衰竭的长程治疗

血管扩张剂用于治疗顽固性心力衰竭,日益增多。口服哌唑嗪有类似硝普钠的作用,可均衡地降低前、后负荷,提高心排出量(Co),降低左室充盈压(LVFP)。近来一些作者报道,连续用哌唑嗪可使其药效减小。为了澄清这个问题,二文均观察了哌唑嗪长程治疗的血液动力学效应。Feldman 对13例严重充血性心力衰竭在服用洋地黄和速尿的过程中,加用了哌唑嗪。于服“首次剂量”、“滴定剂量”[从首次剂量2mg 逐渐增加剂量,直至心排出量不再增加,肺动脉舒张压(PAD)不再下降或平均动脉压(MAP)下降>10毫米汞柱,此时的剂量为滴定剂量,一般为2～5mg,每6～     

C型钠尿肽对妊高征患者的心功能效应及与一氧化氮水平的相关性

目的 :探讨 C型钠尿肽 （CNP）对妊高征 （PIH）患者的心功能效应及与一氧化氮 （NO）水平的相关性。方法 :重度 PIH患者 4 0例随机分为 CNP组及安慰剂对照组 ,每组各 2 0例。分别给予 CNP（6μg/kg）或安慰剂静滴 30 m in。应用美国 Acuson 12 8XP/10型彩色电脑声像仪 ,监测用药前后心功能参数 :每搏输出量 （SV） ,心排出量 （CO） ,左室射血分数 （L VEF） ,心脏指数 （CI） ,心率 （HR）及血压 （BP）的变化 ,并测定静脉血 NO代谢终产物亚硝酸基 /硝酸基（NO2 - /NO3- ）水平。取正常孕妇 4 0例为血流动力学基础值对照组。结果 :PIH组与对照组比较 ,血流动力学参数有增高、降低或正常 ,各参数波动范围明显增加 ,但 CO及 HR均值明显增高 （P<0 .0 5 ）。 CNP治疗 30 m in后平均动脉压 （MAP）下降 （P<0 .0 1） ,SV、CO、CI及 HR均显著下降 （P<0 .0 5 ） ,各参数下降值与基础值呈显著正相关（P<0 .0 1） ,NO2 - /NO3-水平显著增高 （P<0 .0 1） ,但 CO及 HR均无显著相关性 （P>0 .0 5 ）。安慰剂组各参数及NO2 - /NO3- 水平变化差异均无显著意义 （P>0 .0 5 ）。结论 :CNP对 PIH患者的心功能高动力学状态具有降低效应并增加 NO产生 ,但 NO可能不直接参与 CNP对 PIH患者的心功能调节。     

静脉滴注L-精氨酸对充血性心力衰竭患者的急性血流动力学效应

目的：评价充血性心力衰竭患静脉滴注L－精氨酸（L－arg）的急性血流动力学效应,探讨L－arg治疗心力衰竭的机制。方法：36例心力衰竭患（心功能Ⅳ级1例,Ⅲ级24例,Ⅱ1级11例）,以20％L－arg100ml加入5％葡萄糖溶液100ml,1h内恒速静脉滴注,每日1次,连续7d。记录用药后心率、血压变化,并对其中11例患（心功能Ⅲ级8例,Ⅱ级3例）采用有创检查观察血流动力学效应,同时测定用药后血液和尿液一氧化氮（NO）。结果：静脉滴注L－arg5min收缩压、舒张压、收缩压与心率乘积均有显降低（P＜0．05）,最大效应时间10－60min,心率无变化。血流动力学检查结果表明,静脉滴注L－arg可使平均动脉压和体循环阻力、肺动脉压、肺毛细血管嵌压、肺血管阻力显降低（P＜0．05－0．01）,心指数和左心室作功指数显增加（P＜0．01）。用药后尿液NO显升高。结论：心力衰竭患静脉滴注L－arg增加了体内NO,血流动力学明显改善。     

大剂量甲强龙联合保护性通气策略治疗创伤性ARDS的疗效及机制探讨

目的观察大剂量甲强龙联合保护性通气策略治疗严重创伤性急性呼吸窘迫综合征（ARDS）的疗效,并探讨其机制。方法将60例创伤性ARDS患者随机分为A、B两组各30例,均行常规治疗;A组行容量控制通气（VCV）,潮气量10～15 mL/mg;B组VCV潮气量4～6 mL/mg,PEEP 5～12 cmH2O,静推甲强龙5 mg/（kg·h）。分别于入术室（T0）、治疗1 h（T1）、3 h（T2）,记录血流动力学指标并行血气分析;T1、T2时检测肺泡灌洗液（BALF）中的丙二醛（MDA）、NO、诱导型NO合成酶（iNOS）、超氧化物歧化酶（SOD）及髓过氧化物酶（MPO）及骨形态发生蛋白2（BMP-2）mRNA、蛋白。结果与T0时比较,两组SBP、心排血量、心脏指数、左心作功和左心作功指数均显著增高,而HR、外周血管阻力、外周血管阻力指数显著下降,且B组较A组变化更显著,P均〈0.05;与T0时比较,两组氧合指数、pH、SpO2升高,乳酸、PCO2降低,B组较A组氧合指数、SpO2、乳酸变化更明显,P均〈0.05;A组T1、T2时BALF中MDA、NO、iNOS、MPO、BMP-2 mRNA及其蛋白高于B组,而SOD下降,P均〈0.01。结论大剂量甲强龙联合保护性通气策略治疗创伤性ARDS可明显改善其血流动力学及血气指标,该作用与其增加BMP-2表达、抑制肺氧化损伤有关。     

严重慢性心力衰竭长程甲巯丙脯酸(Captopril)治疗的血流动力学效应类型

晚近的研究提示,血管扩张剂的早期和晚期血流动力学效应可能不一致。由于临床表现可能并不真实反映左室功能的变化,需要应用侵入性血流动力学检查来阐明短期和长程治疗效果之间的关系。本文通过侵入性血流动力学检查,研究严重心力衰竭患者短期和长程口服甲巯丙脯酸治疗的血流动力学效应类型。方法:51例洋地黄及利尿剂无效的严重慢性心力衰竭患者,男性38例,女性13例,年龄29～83岁(平均65岁)。心力衰竭原因为缺血性心肌病(31例)、原发性心肌病(17例)、二尖瓣换置术后持久重度左室功能不良(3例)。先作右心插管术测定右房压、肺动脉压及肺毛细血管楔嵌压,桡动脉插管测定体循环压,用热稀释法测定心排出量并连续记录心率。然后给予甲巯丙脯酸25毫克,并每30分钟重     

Signaling pathway of insulin-like growth factor- Ⅱ as a target of molecular therapy for hepatoblastoma

AIM: To address the possibility that insulin-like growth factor (IGF)-II is a growth factor and its signaling pathway so as to develop a molecular therapy for hepatoblastoma. METHODS: Huh-6 and HepG2, human hepatoblastoma cell lines, were used. IGF-II was added to the medium deprived of serum. Western blot analysis was performed to clarify the expression of IGF-I receptor (IGF-IR). Inhibitors of IGF-IR (piclopodophyllin, PPP), phosphatidyl-inositol (PI) 3-kinase (LY294002 and Wortmannin), or mitogen-activated protein (MAP) kinase (PD98059) were added to unveil the signaling pathway of IGF-II. Cells were analyzed morphologically with hematoxylin-eosin staining to reveal the mechanism of suppression of cell proliferation. RESULTS: IGF-II stimulated cells proliferated to 2.7 (269%+/-76%) (mean+/-SD) (Huh-6) and 2.1 (211%+/-85%) times (HepG2). IGF-IR was expressed in Huh-6 and HepG2. PPP suppressed the cell number to 44%+/-11% (Huh-6) and 39%+/-5% (HepG2). LY294002 and Wortmannin suppressed the cell number to 30%+/-5% (Huh-6), 44%+/-0.4% (HepG2), 49%+/-1.0% (Huh-6) and 46%+/-1.1% (HepG2), respectively. PD98059 suppressed the cell number to 33%+/-11% for HepG2 but not for Huh-6. When cell proliferation was prohibited, many Huh-6 and HepG2 cells were dead with pyknotic or fragmented nuclei, suggesting apoptosis. CONCLUSION: IGF-II was shown to be a growth factor of hepatoblastoma via IGF-I receptor and PI3 kinase which were good candidates for target of molecular therapy.     

Signaling pathway of insulin-like growth factor-Ⅱ as a target of molecular therapy for hepatoblastoma

INTRODUCTIONHepatoblastoma(HBL)arises in the liver of infants younger than3years of age[1].The growth factor and its signaling pathway could be revealed so as to develop a novel molecular therapy for HBL.Insulin-like growth factor(IGF)-Ⅱis a hormone that…     

Stilbestrols and stilbestrol derivatives: estrogenic potency and temporal relationships between estrogen receptor binding and uterine growth

This study analyzes some of the differences between the estrogenic potencies of two homo logous stilbestrols, the potent estiogen diethylstilbestrol (DES) and the weak estrogen dimethylstilbestrol (DMS). The action of these compounds and their corresponding dimethyl ethers is compared in terms of the duration of their interaction with the estrogen receptor in immature rat uterus and the time-course of responses elicited in this tissue.Dose-response curves of 3-day uterotrophic assays indicate that etherification of DMS, which is only weakly uterotrophic, converts it into a compound, DMS-(OMe)₂, that has enhanced uterotrophic activity, while etherification of the more active estrogen, DES, diminishes its potency. Only at high doses is DES-(OMe)₂ as effective a uterotrophic agent as DES. After a single injection, DMS (20 μg) and DES (10 μg) both rapidly translocate estrogen receptor from the cytoplasmic to the nuclear compartment, but while uterine weight (by 24 h) and nuclear receptor levels (by 6 h) rapidly return to control levels after DMS, they remain elevated for a more prolonged period after DES. Likewise, DMS stimulates only an early (2 h) wave of uterine deoxyglucose phosphorylation. In contrast to DMS, DMS-(OMe)₂ (20 μg) shows a gradual movement of receptor to the nucleus after 1 h, with moderate but above control levels of receptor being maintained for at least 36–48 h. This retention of nuclear receptor correlates with prolonged elevation of uterine weight (beyond 60 h) and stimulation of deoxyglucose metabolism (beyond 24 h). Likewise a high (10 μg) dose of DES-(OMe)₂ evokes a slower but more protracted elevation of nuclear receptor levels, and a more prolonged elevation of uterine weight than does DES (10 μg).The weak activity of DMS appears to be due to its short duration of interaction with receptor, and conversion to the methyl ether prolongs nuclear receptor occupancy and increases its biological potency. DES is potent because it is itself long-acting. Methylation of DES further extends its period of nuclear receptor occupancy; this increases its duration of action at high doses, but reduces its potency at low doses.     

Signaling pathway of insulin-like growth factor-Ⅱ as a target of molecular therapy for hepatoblastoma

AIM: To address the possibility that insulin-like growth factor (IGF)-Ⅱ is a growth factor and its signaling pathway so as to develop a molecular therapy for hepatoblastoma.METHODS: Huh-6 and HepG2, human hepatoblastoma cell lines, were used. IGF-Ⅱ was added to the medium deprived of serum. Western blot analysis was performed to clarify the expression of IGF-Ⅰ receptor (IGF-IR). Inhibitors of IGF-IR (piclopodophyllin, PPP),phosphatidyl-inositol (PI) 3-kinase (LY294002 and Wortmannin), or mitogen-activated protein (MAP) kinase (PD98059) were added to unveil the signaling pathway of IGF-Ⅱ. Cells were analyzed morphologically with hematoxylin-eosin staining to reveal the mechanism of suppression of cell proliferation.RESULTS: IGF-Ⅱ stimulated cells proliferated to 2.7(269% ± 76%) (mean ± SD) (Huh-6) and 2.1 (211%± 85%) times (HepG2). IGF-IR was expressed in Huh-6 and HepG2. PPP suppressed the cell number to 44% ±11% (Huh-6) and 39% ± 5% (HepG2). LY294002 and Wortmannin suppressed the cell number to 30% ± 5%(Huh-6), 44% ± 0.4% (HepG2), 49% ± 1.0% (Huh-6)and 46% ± 1.1% (HepG2), respectively. PD98059 suppressed the cell number to 33% ± 11% for HepG2 but not for Huh-6. When cell proliferation was prohibited,many Huh-6 and HepG2 cells were dead with pyknotic or fragmented nuclei, suggesting apoptosis.CONCLUSION:IGF- Ⅱ was shown to be a growth factor of hepatoblastoma via IGF-I receptor and PI3 kinase which were good candidates for target of molecular therapy.     

丹参素异丙酯对慢性缺氧大鼠血压和左心室功能的影响

目的: 研究丹参素异丙酯对缺氧大鼠左心室功能的影响。方法: 制备慢性缺氧大鼠模型,分别用大、小剂量的丹参素异丙酯灌胃,设立维拉帕米阳性对照组和正常对照组,采用大鼠心导管插入的方法,测定大鼠血流动力学和心功能指标,观察不同剂量丹参素异丙酯对慢性缺氧大鼠左室心功能的影响。结果: 与正常组比较,单纯模型组的动脉收缩压（SBP）、动脉舒张压（DBP）、平均动脉压（MBP）、左室收缩压（LVSP）、最大上升速率（+dp/dtmax）和最大下降速率（-dp/dtmax）显著升高（P<0.05或P<0.01）,T值(t-dp/dtmax)显著降低（P<0.05）,HE染色显示,心肌细胞出现肌纤维断裂、溶解,细胞核固缩、溶解。与单纯模型组比较,小剂量组的DBP、MBP、心率(HR)、左室舒张末压(LVEDP)和-dp/dtmax显著降低（P<0.05或P<0.01）,T值显著升高（P<0.05）;大剂量组的SBP、DBP、MBP、HR、LVEDP、左室舒张压(LVDP)、+dp/dtmax和-dp/dtmax显著降低（P<0.05或P<0.01）,T值显著升高（P<0.01）;HE染色显示,大、小剂量组心肌细胞内糖元含量丰富,肌纤维排列相对规则,未见明显的肌纤维断裂、溶解及核分裂。与阳性对照组比较,小剂量组的DBP、MBP、LVSP、LVDP和T值显著升高（P<0.05或P<0.01）,LVEDP显著降低（P<0.05）;大剂量组的DBP和T值均显著升高（P<0.05或P<0.01）,LVDP、LVEDP和+dp/dtmax均显著降低（P<0.05或P<0.01）。与小剂量组比较,大剂量组的LVDP、LVEDP和+dp/dtmax均显著降低（P<0.01）。结论: 丹参素异丙酯对慢性缺氧造成的大鼠血压升高、心率加快、心功能亢奋等有明显的抑制作用,因而对缺氧大鼠的心功能有明显的保护作用。     

About GATA3, HNF3A, and XBP1, three genes co-expressed with the oestrogen receptor-alpha gene (ESR1) in breast cancer

The human follitropin (follicle stimulating hormone, FSH) receptor (FSHR) is a G protein-coupled receptor (GPCR). To identify cytoplasmic proteins that may regulate FSHR function, a yeast-based interaction trap was performed. A linked construct of the first and second intracellular loops (iL1-iL2 bait) of FSHR was used as bait and a human ovarian cDNA library was used as prey. Among the proteins identified that interacted with the bait was 14-3-3τ, a member of a family of homodimeric cytoplasmic adapter proteins. Human granulosa cells, the site of FSHR expression in the ovary, were found to contain 14-3-3τ. Importantly, 14-3-3τ co-immunoprecipitated with FSHR stably expressed in HEK 293 cells. Its association with FSHR was follitropin-dependent. Over-expression of 14-3-3τ resulted in a modest decrease of follitropin-induced cAMP accumulation. Collectively, these data support a role for 14-3-3τ in follitropin action. The finding that 14-3-3τ interacts with FSHR is novel and should lead to new insights into the regulation of GPCR in general and FSHR specifically.     

毛细支气管炎患儿血清25-（OH）-D3水平、尿LTE4水平变化的临床意义及维生素D3干预对尿LTE4的影响0976

目的：探讨毛细支气管炎患儿血清25-( OH)-D3水平、尿LTE4水平变化的临床意义及维生素D3干预对尿LTE4的影响。方法选择毛细支气管炎急性期患儿76例作为毛细支气管炎组,另选取同期在我院儿童保健门诊体检的60例健康儿童作为对照组。毛细支气管炎组患儿给予常规治疗,进入恢复期后,随机分为维生素D3干预组和未干预组,每组各38例,干预组予维生素D3滴剂400IU/天口服,未干预组不予处理,随访6个月。分别于入院次日(急性期)、维生素D3干预前一日(恢复期)检测各组患儿血清25-( OH)-D3和尿LTE4水平,并干预6个月后检测干预组及未干预组尿LTE4水平。结果毛细支气管炎重型及轻型患儿血清25-( OH)-D3水平均明显低于对照组;而尿LTE4则明显高于对照组;重型患儿血清25-( OH)-D3水平明显低于轻型患儿,尿LTE4水平明显高于轻型(P<0．05);急性期及恢复期血清25-(OH)-D3水平均低于对照组,尿LTE4水平明显高于对照组;急性期25-( OH)-D3水平明显低于恢复期;尿LTE4水平则明显高于恢复期(P均<0．01)。血清25-(OH)-D3与毛细支气管炎病情轻重呈负相关(r=-0．68,P<0．01),尿LTE4与病情轻重呈正相关(r=0．76,P<0．01);血清25-(OH)-D3与尿LTE4呈负相关(r=-0．63,P<0．05)。干预后,干预组及未干预组尿LTE4水平比较,两组之间差异无统计学意义( P>0．05)。结论毛细支气管炎患儿急性期维生素D3干预对尿LTE4无下调作用。     

溴氰菊酯和三氯杀虫酯现场灭蛉效果观察

用2.5％可湿性溴氰菊酯和国产三氯杀虫酯(7504)进行现场喷洒灭蛉结果表明,每平方米墙面使用溴氰菊酯37.5mg、25mg和12.5mg剂量,可使白蛉数量比对照区降低13—19倍,削平季节高峰。当年的灭蛉效果超过50％的可湿性DDT。在模拟土墙和泸纸药膜上,残效至少可达50天以上。建议以每平方米12.5mg作为灭蛉喷洒剂量推广使用;7504每平方米1g的剂量可使白蛉数量降低8.9倍,值得进一步试用,但其剂型应研究改进。连续观察证明,在当地条件下,于喷洒后第三年白蛉密度可恢复到具有流行病学意义的程度。     

Inhibition of transient lower esophageal sphincter relaxation and gastroesophageal reflux by metabotropic glutamate receptor ligands

BACKGROUND & AIMS: Transient lower esophageal sphincter relaxation (TLESR) is the major mechanism of gastroesophageal acid reflux. TLESR is mediated via vagal pathways, which may be modulated by metabotropic glutamate receptors (mGluRs). Group I mGluRs (mGluR1 and 5) have excitatory effects on neurons, whereas group II (mGluR2 and 3) and group III (mGluR4, 6, 7, and 8) are inhibitory. This study determined the effect of mGluRs on triggering of TLESR and reflux in an established conscious ferret model. METHODS: Esophageal manometric/pH studies were performed in ferrets with chronic esophagostomies. TLESR were induced by a gastric load of 25 mL glucose (pH 3.5) and 30 mL air. RESULTS: In control treated animals, gastric load induced 3.52 +/- 0.46 TLESRs per 47-minute study, 89.7% of which were associated with reflux episodes (n = 16). The mGluR5 antagonist MPEP inhibited TLESR dose dependently, with maximal 71% +/- 7% inhibition at 35 micromol/kg (n = 9; P < .0001). MPEP also significantly reduced reflux episodes (P < .001) and increased basal lower esophageal sphincter pressure (P < .05). MPEP inhibited swallowing dose dependently, suggesting a common action on trigger mechanisms for swallowing and TLESR. The more selective analogue, MTEP, had more potent effects (90% +/- 6% inhibition TLESR at 40 micromol/kg; n = 8; P < .0001). In contrast, the group I agonist DHPG tended to increase TLESR. The group II agonist (2R, 4R)-APDC was ineffective, whereas the group III agonist L-(AP4 slightly reduced TLESR (33% at 11 micromol/kg; P < .05). The selective mGluR8 agonist (S)-3, 4-DCPG inhibited TLESR by 54% at 15 micromol/kg (P < .01). CONCLUSIONS: mGluR5 antagonists potently inhibit TLESR and reflux in ferrets, implicating mGluR5 in the mechanism of TLESR. mGluR5 antagonists are therefore promising as therapy for patients with GERD.