超高效液相色谱-三重四极杆质谱法测定不同银杏叶制剂中13个黄酮类成分

目的 运用超高效液相色谱串联三重四极杆质谱（HPLC-QQQ）建立一种能够同时测定银杏叶制剂中13个黄酮类成分的分析方法。方法 采用Agilent Poroshell 120 EC-C₁₈色谱柱（50 mm×3.0 mm,2.7 μm）,以0.1%甲酸溶液-乙腈为流动相,梯度洗脱,体积流量0.3 mL/min,柱温30℃。在电喷雾离子化负离子模式下离子化,以多反应监测方式（MRM）检测。结果 13种黄酮类成分芦丁、异槲皮苷、槲皮素-3-O-β-D-葡萄糖基（1→2）-α-L-鼠李糖苷、山柰酚-3-O-芸香糖苷、水仙苷、槲皮苷、芹菜素-7-O-β-D-吡喃葡萄糖苷、木犀草素、槲皮素、芹菜素、山柰酚、异鼠李素、芫花素的分离度良好,在各自的质量浓度范围内的线性关系良好（r=0.999 0）,且精密度试验、重复性试验的RSD值均小于3.5%,供试品溶液在12 h内稳定性好,各成分的平均回收率在94.5%~100.5%。不同批次样品之间,总黄酮含量相差不大;各批次的银杏黄酮类成分含量均不相同,差异较大,其中黄酮苷类化合物所占比例相对较大,芦丁、水仙苷含量均较单糖（异槲皮苷、槲皮苷）含量高,芫花素、木犀草素等黄酮苷元含量最低。结论 方法分离度好、操作简便、专属性强,能够明确反映出银杏叶提取物中13个黄酮类成分的分布和差异,可用于银杏叶提取物制剂的质量控制。     

基于化学计量学的指纹图谱法鉴别金线莲及其混伪品

目的 建立金线莲高效液相色谱（high performance liquid chromatography,HPLC）指纹图谱分析方法,基于化学计量学对比区分其7种常见混伪品（台湾银线兰、长片金线兰、滇越金线兰、丽蕾金线兰、血叶兰、斑叶兰、虎耳草）,为其真伪鉴别提供技术参考。方法 采用Welch Ultimate XB-C₁₈ 色谱柱（4.6 mm×250 mm,5 μm）,流动相乙腈（A）-0.1%甲酸水（B）,梯度洗脱60 min,流速1.0 mL·min^-1,柱温30 ℃,检测波长360 nm,进样量10 μL。建立17批金线莲的指纹图谱,通过聚类分析、主成分分析（principal component analysis,PCA）和正交偏最小二乘判别分析（orthogonal partial least square-discriminate analysis,OPLS-DA）用于区分台湾银线兰、长片金线兰、滇越金线兰、丽蕾金线兰、血叶兰、斑叶兰、虎耳草共7种混伪品。结果 建立了金线莲高效液相色谱指纹图谱,确定了16个共有峰（指认11个成分：槲皮素3,7-二葡萄糖苷、异鼠李素-3-O-芸香糖苷-7-O葡萄糖苷、芦丁、异槲皮苷、山柰酚-3-O-芸香糖苷、水仙苷、紫云英苷、异鼠李素-3-O-葡萄糖苷、槲皮素、山柰酚、异鼠李素）,17批金线莲与对照指纹图谱的相似度均＞0.85,7种混伪品与金线莲对照指纹图谱的相似度均＜0.8,通过正交偏最小二乘判别分析筛选出金线莲与混伪品的差异标志物为水仙苷,对差异标志物进行含量验证,金线莲中水仙苷含量（高于1 098.09 μg·g^-1）显著高于其混伪品（低于379.96 μg·g^-1）。结论 高效液相色谱指纹图谱的方法简单、可靠,可用于金线莲与混伪品的区分,水仙苷可以作为区分混伪品的标志物之一。     

用HPLC法同时测定养血安神糖浆中4种成分的含量

目的 建立同时测定养血安神糖浆中槲皮苷、木犀草苷、芦丁和2,3,5,4’-四羟基二苯乙烯-2-O-β-D-葡萄糖苷含量的方法。方法 采用HPLC法。色谱柱为Waters Symmetry C₁₈（4.6 mm×250 mm,5 μm）。流动相：0.1%醋酸（A）-甲醇（B）梯度洗脱,0～15 min,95%～90%A;15～35 min,90%～70%A;35～55 min,70%～60%A;55～85 min,60%～50%A;85～95 min,10%A。流速：1.0 ml/min,检测波长：256 nm和320 nm,柱温30 ℃,进样量10 μl。结果 槲皮苷、木犀草苷、芦丁和2,3,5,4’-四羟基二苯乙烯-2-O-β-D-葡萄糖苷分别在10～300、5.0～150.0、5.0～150.0、20.0～600.0 μg/ml范围呈良好的线性关系（r≥0.9989）;加样回收率分别为（96.75±1.41）%、（99.61±1.01）%、（97.18±1.96）%和（99.12±0.97）%（n = 6）。结论 该方法简单、准确、稳定,可同时测定养血安神糖浆中4种成分的含量。     

基于HPLC多组分定量联合化学计量学及灰色关联度分析的地肤子质量控制研究

目的 建立定量检测地肤子中9种成分含量的高效液相色谱（HPLC）法,并联合化学计量学及灰色关联度分析对其质量控制进行研究。方法 采用 HPLC法同时检测地肤子中芦丁、金丝桃苷、异鼠李素-3-O-葡萄糖苷、槲皮素、异鼠李素、齐墩果酸、胡萝卜苷、地肤子皂苷Ⅰc、β-谷甾醇含量,并通过聚类分析、主成分分析、正交偏最小二乘法-判别分析及灰色关联度分析比较不同产地地肤子质量差异。结果 芦丁、金丝桃苷、异鼠李素-3-O-葡萄糖苷、槲皮素、异鼠李素、齐墩果酸、胡萝卜苷、地肤子皂苷Ⅰc和β-谷甾醇分别在各自范围内线性关系良好（r＞0.999 2）;精密度、稳定性及重复性良好;平均加样回收率在96.93%～100.12%。聚类分析结果显示17批样品聚为3类;主成分分析结果显示主成分1、2是影响样品质量评价的主要因子;正交偏最小二乘法-判别分析结果显示地肤子皂苷Ⅰc、芦丁和齐墩果酸变量重要性投影（VIP）值均＞1,是影响产品质量差异的标志性成分;灰色关联度分析结果显示17批样品的相对关联度在0.334 0～0.622 5,不同产地地肤子质量存在一定差异。结论 所建立的HPLC多组分定量联合化学计量学及灰色关联度分析方法操作便捷、结果准确,可为地肤子质量控制和品质评价提供依据。     

新疆白刺叶中异鼠李素-3-芸香糖苷的含量分析

目的 分析新疆产白刺叶中黄酮类成分异鼠李素-3-芸香糖苷的含量,对新疆白刺的品质评价和质量控制提供依据。方法 采用HPLC法对新疆白刺叶中异鼠李素-3-芸香糖苷进行含量分析。色谱柱：Diamonsil C₁₈柱（4.6 mm×250 mm,5 μm）;流速：1 ml/min;柱温：26℃;检测波长：360 nm。结果 新疆白刺叶中异鼠李素-3-芸香糖苷在0.007 813~1 mg/ml的范围内线性关系良好,平均加样回收率为100.13%,RSD=3.02%。结论 异鼠李素-3-芸香糖苷在白刺叶中的含量存在较大的种内和种间差异。该方法操作简单,检测结果准确,重复性好,可作为新疆白刺叶中异鼠李素-3-芸香糖苷的定量分析方法。     

RP-HPLC法同时测定茵陈中5种化学成分的含量

目的建立同时测定茵陈中芦丁、金丝桃苷、异槲皮苷、4,5-O-二咖啡酰奎宁酸、异鼠李素-3-O-葡萄糖苷含量的方法,为茵陈药材的质量控制提供依据。方法采用RP-HPLC法。色谱柱:LunaC18柱(250 mm×4.6 mm,5μm);流动相:乙腈-体积分数0.04%磷酸水溶液(体积比17∶83);检测波长:345 nm。结果芦丁、金丝桃苷、异槲皮苷、4,5-O-二咖啡酰奎宁酸、异鼠李素-3-O-葡萄糖苷质量浓度分别在0.942~18.84 mg.L-1(r=0.9995)、1.190~23.79 mg.L-1(r=0.9995)、1.107~22.14 mg.L-1(r=0.9994)、56.78~1.136×103mg.L-1(r=0.9990)、0.621 9~12.44 mg.L-1(r=0.9998)内与峰面积呈良好的线性关系(n=5);方法回收率(n=9)分别为98.1%、100.7%、98.4%、100.2%、101.7%。结论该方法可用于茵陈药材的质量控制。     

苗药水冬瓜叶化学成分的HPLC-HESI-HRMS分析

目的 采用HPLC-HESI-HRMS技术对苗药水冬瓜叶中的化学成分进行定性分析。方法 采用Thermo Fisher Hypersil GOLD aQ C₁₈色谱柱（100 mm×2.1 mm，1.9 μm），以0.1%甲酸水溶液-乙腈（0.1%甲酸）为流动相梯度洗脱；质谱使用HESI离子源，正离子和负离子模式下采集数据。同时采用HPLC比较7-羟基香豆素、断氧化马钱苷、金丝桃苷、异槲皮苷对照品与样品中化合物17，20，24，25保留时间（t_R）差异性，比较薄层色谱荧光特征与比移值（Rf值），并参考文献中有关7-羟基香豆素、断氧化马钱苷、金丝桃苷、异槲皮苷质谱裂解碎片特征综合进行验证。结果 通过高分辨质谱正、负离子质谱信息、数据库及相关文献数据对照，共推测出苗药水冬瓜叶中38个化合物，包括3个氨基酸类化合物，5个生物碱类化合物，10个有机酸类化合物，3个苯丙素类化合物，3个芳香含氧衍生物类化合物，3个萜类化合物，6个黄酮类化合物，1个酰胺类化合物，4个其他类化合物。验证结果表明，7-羟基香豆素、断氧化马钱苷、金丝桃苷、异槲皮苷对照品分别与化合物17，20，24，25的t_R相比差异均<0.1 min；在药材样品溶液、7-羟基香豆素、断氧化马钱苷、金丝桃苷、异槲皮苷对照品色谱相应的位置上分别显相同颜色的蓝色荧光斑点，Rf值一致；文献表明化合物17，20，24，25分别与7-羟基香豆素、断氧化马钱苷、金丝桃苷、异槲皮苷具有相似的质谱裂解碎片特征。结论 初步鉴定出化合物17，20，24，25分别为7-羟基香豆素、断氧化马钱苷、金丝桃苷、异槲皮苷。HPLC-HESI-HRMS对苗药水冬瓜叶中化学成分的初步推测具有一定的科学性，为阐明苗药水冬瓜叶药材的药效物质基础提供依据。     

用HPLC法测定红茴香注射液中槲皮苷的含量

目的 建立高效液相色谱法测定红茴香注射液中槲皮苷的含量。方法 色谱柱为Dikma C₁₈(250 mm×4.6 mm,5 μm),以乙腈-0.1%磷酸水溶液（25∶75）为流动相,流速为1.0 ml/min,柱温30 ℃,检测波长为256 nm。结果 槲皮苷在0.215～3.225 μg范围内呈良好线性关系,相关系数为0.999 6,该法的平均回收率为99.39%,RSD为0.82%（n=6）,重复性为1.194 mg/ml,RSD为0.40%。结论 3批红茴香注射液的槲皮苷平均含量结果为1.191 mg/ml,该法简便、快速、准确, 可作为测定红茴香注射液中槲皮苷含量的方法。     

畲药降脂轻身茶的HPLC特征图谱及4个成分含量测定

目的 采用HPLC建立畲药降脂轻身茶的特征图谱,并同时测定4种成分的含量。方法 以绿原酸、芦丁、异槲皮苷和山奈酚-3-O-芸香糖苷为对照品;采用Agilent ZORBAX SB-C₁₈色谱柱（250 mm×4.6 mm,5 μm）,流动相为乙腈-0.2%磷酸溶液,线性梯度洗脱,流速为0.8 mL·min^-1,检测波长为360 nm,柱温为40℃。采用中药色谱指纹图谱相似度评价系统对结果进行分析。结果 绿原酸、芦丁、异槲皮苷、山奈酚-3-O芸香糖苷分别在0.072 6~0.726,0.076 3~0.763,0.071~0.71,0.113 1~1.131 μg内呈良好的线性关系,相关系数均≥ 0.999 6;平均加样回收率分别为96.15%,95.62%,95.28%,95.76%。结论 所建立的特征图谱相关性强,可结合4种成分含量测定全面控制畲药降脂轻身茶的质量。     

HPLC同时测定三叶青中5种黄酮类成分的含量

目的 建立HPLC同时测定三叶青中5个黄酮类化合物芦丁、异槲皮苷、山奈酚-3-O-芸香糖苷、槲皮素和山奈酚的含量。方法 Agilent ZORBAX SB-C₁₈色谱柱（250 mm×4.6 mm,5 μm）;流动相为乙腈-0.2%磷酸溶液,梯度洗脱,流速为1.0 mL·min^-1,检测波长为360 nm,柱温为35℃。结果 芦丁、异槲皮苷、山奈酚-3-O-芸香糖苷、槲皮素和山奈酚分别在0.087 8~0.878 μg、0.069 6~0.696 μg、0.162 9~1.629 μg、0.002 7~0.027 μg、0.007 23~0.072 3 μg内与峰面积呈良好的线性关系,r ≥ 0.999 7;平均加样回收率分别为97.44%,96.88%,97.00%,96.42%,96.24%。结论 该方法简便、高效,可作为三叶青的质量控制提供参考。     

Synthesis and evaluation of 2,6-piperidinedione derivatives as potentially novel compounds with analgesic and other CNS activities

New 2,6-piperidinediones 2_a–g and 4_a–d were prepared by initial condensation of aromatic aldehydes or cycloalkanones with cyanoacetamide to give α-cyanocinnamides l_a–g or cycloalkylidenes 3_a,b which underwent Michae1 addition with ethyl cyanoacetate or diethylmalonate. Compounds 4_a–d were alkylated by various alkyl halides to produce the N-alkylated 2,6-piperidinedione derivatives 5_a–m. Some new selected compounds 2_a–c,f, 4_a–d & 5_e,h,j were pharmacologically evaluated for potential anticonvulsant, sedative and analgesic activities. These compounds exhibited significant anticonvulsant and analgesic effects after a single I.P. administration 100 mg/kg b.wt. . On the other hand all the investigated compounds induced hypnotic activity and prolonged the phenobarbital sodium- induced sleep as compared with the control group and the most potent compound was found to be 2_f.     

NEURAMIDE STIMULATES ADRENOCORTICOTROPIN BUT NOT PROLACTIN RELEASE FROM RAT PITUITARY

Neuramide (NMD), a substance found in crude preparations of porcine stomach extract, is a viral inhibitor that also has putative immunostimulatory effects. The effects of NMD on stress-hormone (ACTH and prolactin—PRL) release were assessed inin vivoandin vitrostudies. In the former, blood levels of corticosterone and PRL were measured in NMD-treated male rats.In vitroexperiments were performed to evaluate the effects of NMD and three of its fractions (obtained with high performance liquid chromatography) on ACTH and PRL release from perfused rat pituitary slices. NMD increased plasma corticosterone levelsin vivoand produced dose-dependent increases inin vitropituitary release of ACTH. No effects on PRL secretion were observedin vivoorin vitro. The stimulatory effects on ACTH release were caused by the NMD fraction with a molecular weight of >5000<10000Da.     

EFFECT OF POLICOSANOL SUCCESSIVE DOSE INCREASES ON PLATELET AGGREGATION IN HEALTHY VOLUNTEERS

Policosanol is a cholesterol-lowering drug with hypocholesterolemic effects demonstrated in experimental models, healthy volunteers and type II hypercholesterolemic patients. In addition, antiplatelet effects of policosanol have been shown in experimental models and healthy volunteers. The effect of successively increasing doses of policosanol on platelet aggregation was investigated in a randomized, placebo-controlled, double-blind study conducted in 37 healthy volunteers. The volunteers were on a placebo-baseline period (two tablets per day) for 7 days and thereafter they received randomly, under double-blind conditions, placebo or policosanol (10mgday⁻¹) for 7 days. After this period dosage was doubled to 20mgday⁻¹for the next 7 days and then again doubled to 40mgday⁻¹, while the control group received placebo tablets all the time. Platelet aggregation as well as coagulation time was measured at baseline and after each dosing step. Results showed that antiplatelet effects of policosanol were successfully enhanced throughout the study, thus suggesting a dose-dependent relationship. No significant effect was reached during the first dosing period, but significant reductions of epinephrine and ADP-induced platelet aggregation were observed after the second one. Finally, a significant inhibition of platelet aggregation induced by all the agonists was observed at the last dosing step. Coagulation time remained unchanged during the trial.     

INDIRECT PARASYMPATHOMIMETIC ACTIVITY OF THE CLASS III ANTIARRHYTHMIC SUBSTANCE / -SOTALOLIN VITRO: REVERSIBLE INHIBITION OF CHOLINESTERASE ISOENZYMES FROM BLOOD AND THE HUMAN CENTRAL NERVOUS SYSTEM

Inhibitory effects of the class III antiarrhythmic compound / -sotalol on acetylcholinesterase (AChE; EC 3.1.1.7) isoenzymes of both erythrocytes and the human caudate nucleus and on serum cholinesterase (ChE; EC 3.1.1.8) were studiedin vitrousing a spectrophotometric kinetic assay with acetylthiocholine (ASCh) as substrate. Sotalol concentrations in the assays varied from 0.32 to 3.2m . All isoenzymes studied were inhibited by / -sotalol in a reversible and concentration-dependent manner. Double reciprocal plots of the reaction velocity against varying ASCh concentrations revealed that / -sotalol reduced substrate affinity (apparent Michaelis constant, KM, increased) of serum ChE, but did not change the enzyme's maximal rate of ASCh hydrolysis (V_max). Thus, / -sotalol inhibition of serum ChE was of the competitive type (rate constant for reversible competitive inhibition: K_i=0.51m ). In contrast, / sotalol reduced the maximal reaction velocity of the AChE isoenzyme from the central nervous system (caudate nucleus), but had no influence on substrate affinity of the enzyme (K_Mwith ASCh unchanged) indicating purely non-competitive inhibition kinetics (rate constant of reversible non-competitive inhibition: K_i′=0.44m ). / -sotalol inhibition of erythrocyte AChE was of mixed competitive/non-competitive type (K_i=0.31m , K_i′=0.49m ). Non-competitive / -sotalol inhibition of caudate nucleus AChE and the non-competitive component of erythrocyte AChE inhibition cannot be overcome by increased concentrations of the cholinergic transmitter acetylcholine (ACh). Peak / -sotalol plasma levels as described in the literature for both humans (15μ ) and experimental animals (dogs: 18μ ; rats: 260μ ) as well as maximal myocardial concentrations of the substance (dogs: 46μ ; rats: 478μ ) are in the range of about 2% to 100% of the sotalol inhibition rate constants determined in the present paper for cholinesterase isoenzymesin vitro. Thus, / -sotalol inhibition of ACh hydrolysisin vivomay contribute to both the well known antiarrhythmic potential and proarrhythmic side effects of the compound.     

鼻渊净胶囊的HPLC指纹图谱研究

目的 建立鼻渊净胶囊的高效液相色谱（HPLC）指纹图谱。方法 采用Agilent SB-C₁₈（4.6 mm×250 mm,5 μm）色谱柱,乙腈-水为流动相、以1.0 ml/min流速行梯度洗脱,检测波长210 nm,柱温30 ℃,洗脱时间为80 min。采用中药色谱指纹图谱相似度评价系统（2004A版）对检测出色谱进行指纹图谱相似度评价。结果 建立了鼻渊净胶囊的HPLC指纹图谱,确定了20个共有峰,15个峰归属到各药材,其中5个峰确认了化学成分;10批样品的指纹图谱的整体相似度与对照图谱比较,均在90%以上。结论 所建立的鼻渊净胶囊指纹图谱有助于从整体上控制该制剂的质量。     

Investigation of the prevalence of tetQ, tetX and tetX1 genes in Bacteroides strains with elevated tigecycline minimum inhibitory concentrations

In this study, the antibiotic susceptibilities to tigecycline and tetracycline of 35 selected Bacteroides fragilis group strains were determined by Etest, and the presence of tetQ, tetX, tetX1 and ermF genes was investigated by polymerase chain reaction (PCR). tetQ was detected in all 12 B. fragilis group isolates (100%) exhibiting elevated tigecycline minimum inhibitory concentrations (MICs) (≥8 μg/mL) as well as the 8 strains (100%) with a tigecycline MIC of 4 μg/mL, whilst tetX and tetX1 were present in 15% and 75% of these strains, respectively. All of these strains were fully resistant to tetracycline (MIC ≥ 16 μg/mL). On the other hand, amongst the group of strains with tigecycline MICs < 4 μg/mL (15 isolates), tetQ, tetX and tetX1 were found less frequently (73.3%, 13.3% and 46.7%, respectively). All but two strains harbouring the tetQ gene in this group were non-susceptible to tetracycline, with a MIC > 4 μg/mL. These data suggest that in most cases tigecycline overcomes the tetracycline resistance mechanisms frequently observed in Bacteroides strains. However, the presence of tetX and tetX1 genes in some of the strains exhibiting elevated MICs for tigecycline draws attention to the possible development and spread of resistance to this antibiotic agent amongst Bacteroides strains. The common occurrence of ermF, tetX, tetX1 and tetQ genes together predicted the presence of the CTnDOT-like Bacteroides conjugative transposon in this collection of Bacteroides strains.     

AMELIORIATION OF CHEMICALLY-INDUCED HEPATOCYTE INJURY BY CYCLOSPORINE A

Cyclosporine A, beside its current applications, possesses potential hepatoprotective effects. This study was directed to investigate the effect of Cyclosporine A pretreatment on hepatic injury due to carbon tetrachloride (CCl₄) and -galactosamine. Rats were injected by two successive doses of Cyclosporine A (5mgkg⁻¹day⁻¹). Six hours after the second dose, 1mlkg⁻¹of CCl₄was administered i.p. Effects associated with Cyclosporine A pretreatment were examined by using isolated hepatocytes and hepatocytes that were immobilized and continuously perfused. -Galactosamine (5m ) was added directly to the perfusion medium. After isolation, hepatocytes were examined histologically by light and electron microscopy, immobilized and perfused for further metabolic functional activity evaluation. Cyclosporine A pretreatmentin vivoproduced hepatoameliorative effects of various degrees which were statistically significant as manifested by: (1) an increased trypan blue exclusion after CCl₄; (2) an improved ureagenesis after CCl₄; (3) a reduction in the lipid droplets accumulation in the cytoplasm produced by CCl₄administration; (4) well preserved cytoplasmic organelles as mitochondria, endoplasmic reticulum ER, nuclear chromatin structures that were altered by CCl₄; and (5) an increased hepatocytes survival in the agarose gel matrix, reduction of LD leakage and improvement of ureagenesis after -galactosamine addition to the perfusion medium. The beneficial effect of Cyclosporine A pretreatment in modifying hepatotoxicity of chemical insults merits further studies.     

喙果黑面神化学成分研究

目的研究大戟科植物喙果黑面神(Breynia rostrata Merr.)的化学成分。方法利用硅胶、凝胶等色谱技术分离纯化化学成分,根据化合物的理化性质和光谱数据进行结构鉴定。结果从喙果黑面神的正丁醇萃取部分分离得到4个化合物,分别鉴定为6-O-甲基丙酰基-α-D-吡喃葡糖(6-O-methylpropanoyl-α-D-glucopyranose,1);4″-苯酚基-6-O-甲基丙酰基-β-D-吡喃葡糖苷(4″-phenolic-6-O-methylpropanoyl-β-D-glucopyranoside,2);1-O-没食子酰基-β-D-吡喃葡糖苷(1-O-galloyl-β-D-glucopyranoside,3);熊果苷(arbutin,4)。结论化合物1和2为新化合物,3和4均为首次从该种植物分离得到。     

EFFECTS OF 2-GUANIDINE-4-METHYLQUINAZOLINE ON GASTRIC ACID SECRETION IN RATS

In this study 2-guanidine-4-methylquinazoline (2-GMQ) appeared to decrease basal and stimulated gastric acid secretion, while structurally related compounds as dimethyl- biguanide, cyanoguanidine and 2-cyanoamino-4-methylpyrymidine did not. Thus, there is an antisecretory effect when the biguanide group is associated with a lipophilic structure. The antisecretive effects exerted by 2-GMQ are associated with anti H₂-histamine activity.The anti H₂-histamine nature of the effects of 2-GMQ was confirmed by the capacity of this compound of depressing the chronotropic activity of the isolated guinea pig auricle increased by histamine, as well as relaxant activity in rat uterus contracted by histamine, since both preparations are rich in H₂-histamine receptors.     

Effect of bay K 8644, a calcium channel agonist,on dog cardiac muscarinic receptors

To investigate further whether the effects of the dihydropyridine (DHP) drugs on calcium channels are related to those of these drugs on muscarinic receptors, the binding characteristics of the DHP calcium channel agonist, Bay K 8644, on muscarinic receptors and calcium channels were compared to those of the DHP calcium channel antagonists, nicardipine and nimodipine in the dog cardiac sarcolemma. Bay K 8644, nicardipine and nimodipine inhibited the specific [³H]QNB binding with K _i values of 16.7μM, 3.5μM and 15.5μM respectively. Saturation data of [³H]QNB binding in the presence of these DHP drugs showed this inhibition to be competitive. Bay K 8644, like nicardipine and nimodipine, blocked the binding of [³H]nitrendipine to the high affinity DHP binding sites, but atropine did not, indicating that the muscarinic receptors and the DHP binding sites on calcium channels are distinct. The K _i value of Bay K 8644 for the DHP binding sites was 4 nM. Nicardipine and nimodipine (K _i :0.1–0.2 nM) were at least 20 times more potent than Bay K 8644 in inhibiting [³H]nitrendipine binding. Thus, the muscarinic receptors were about 4000 times less sensitive than these high affinity DHP binding sites to Bay K 8644. These results suggest that the DHP calcium agonist Bay K 8644 binds directly to the muscarinic receptors but its interaction with the muscarinic receptors is not related to its binding to the DHP binding sites on calcium channels.