肾上腺素能受体研究的新进展

肾上腺素能受体(以下简称受体)的亚型β受体的β_1(心脏和脂肪组织)和β_2(平滑肌)两种亚型均可与腺苷环化酶相偶联。前一亚型的拮抗剂为 metoprolol 和心得宁;后一亚型的拮抗剂为 butoxamine。α_1受体即突触后α受体,儿茶酚胺作用时可引起血管及其他平滑肌收缩以及肝脏某些代谢作用;α_2受体存在于突触前及突触后各部位。对突触前α受体的研究,阐明了儿茶酚胺反馈性抑制交感神经末梢释放去甲肾上腺素,由于它对某些激动剂如氯压啶和拮抗剂育亨宾有较大的亲和力,因此它与典型的突触后α受体在药理学上有明显     

β3肾上腺素能受体激动剂的减肥作用

β3肾上腺素能受体(β3-adrenoreceptor,β3-AR)主要分布在白色和棕色脂肪细胞上,β3-AR激动剂与之结合可刺激白色脂肪组织分解、棕色脂肪组织非颤栗产热,提高脂肪氧化和能量消耗而减轻体重。     

蛇床子素对家兔主动脉条的钙拮抗作用

蛇床子素30μmol·L~(-1)及100μmol·L~(-1)使NE、CaCl_2和高K~+除极化所致的家兔主动脉条收缩量—效曲线右移,最大反应降低.表明蛇床子素有松弛血管平滑肌作用,并与Ca~(2+)呈非竞争性拮抗作用.和阻滞α受体或激动β受体无关;选择性作用于电位依赖性Ca~(2+)通道,抑制细胞外Ca~(2+)内流;在100μmol·L~(-1)时,明显减弱NE诱导的依赖细胞内Ca~(2+)收缩。证明蛇床子素松弛血管平滑肌作用可能与其Ca~(2+)拮抗作用有关。     

葛根对β-肾上腺素能受体阻滞作用的研究

本文报告了葛根浸膏具有较为广泛而显著的β-受体阻滞效应。且对β_1-受体的作用强于β_2-受体。 相当于0.5～5mg/ml或750mg/kg的葛根能分别对抗异丙肾上腺素0.17～1.7μg/ml或10μg/kg诱发的离体或在体心脏的兴奋作用。此外,相当于750mg/kg的葛根除能阻滞10μg/kg异丙肾上腺素及肾上腺素舒血管(β-受体效应)所致的降压作用外,尚能降低正常心率(平均下降43.7％)及血压(平均下降40±6mmHg)的作用,这些结果为葛根用来缓解心绞痛,治疗快速型心律失常及高血压等提供了根据。 将葛根(750mg/kg)与心得宁(0.1mg/kg)抗异丙肾上腺素(10μg/kg)所致的β-受体效应加以比较,表明两者作用大体相似,减慢心率的作用心得宁似乎稍强于葛根。降压作用葛根略优于心得宁,且葛根无明显的抑制心脏的作用。 根据上述事实,可以认为葛根是一种有效的β-受体阻滞剂。     

β-肾上腺素能受体

交感神经兴奋时,末梢释放的递质儿茶酚胺作用于效应器官细胞,引起一系列生理活动和生化反应。已发现许多具有特定分子结构的激动剂和阻滞剂虽用量极微,但能对相应的组织和器官产生显著的药理作用。为解释这些现象,提出了药物作用的受体学说。受体学说认为,药物是先通过与细胞的一些特殊受体发生     

米帕林对β－肾上腺素能受体的作用

米帕林对β－肾上腺素能受体的作用邢成，季少平，王鲁明，吕宝璋（北京军事医学科学院基础医学研究所，北京１００８５０）米帕林（ｍｅｐａｃｒｉｎｅ，Ｍｅｐ）是磷脂酶Ａ，及磷脂酶Ｃ的抑制剂，也是一种膜稳定剂［１］．我们曾证实它在磷脂代谢和对β－肾上腺素能受体...     

麻黄碱对单胺氧化酶活性的影响

麻黄碱于体外抑制单胺氧化酶的最低有效浓度为20毫克分子,其抑制强度約为异丙异烟肼的1/20。于体內不論麻黄碱4毫克/公斤一次,或每隔半小时一次,共五次,总量为20毫克/公斤,对单胺氧化酶都无影响。     

低效价肝素对兔主动脉壁摄取125Ⅰ-胆固醇的影响

低效价肝素(38 U/mg)50 mg/kg,给家兔iv,可抑制兔主动脉壁摄取¹²⁵I—CH,在第12h,抑制率为53%,对已被去甲肾上腺素损伤的动脉内皮,肝素仍可降低主动脉壁¹²⁵I-CH的摄取量,抑制率为34.6%。iv¹²⁵I-CH 50μCi/kg 12 h后,备组血中¹²⁵I-CH的cpm无显著差异。但动脉壁与血中cpm的比值差异非常显著,一次iv后,肝素降低动脉内皮通透性的作用可持续24h以上。     

盐酸小檗胺松弛离体兔肾动脉条作用原理的研究

盐酸小檗胺能松弛去甲肾上腺素、高钾和钙剂引起的兔肾动脉条的收缩,并使量效曲线右移,最大反应降低。它松弛肾动脉条的原理与维拉帕米相似,是通过拮抗钙而实现的。其拮抗参数pD’_2值为4.76,而维拉帕米为5.68,故可认为盐酸小檗胺为非竞争型钙拮抗剂,拮抗强度比维拉帕米弱。     

EFFECT OF cGMP INHIBITORS ON THE ACTIONS OF NITRODILATORS IN RAT AORTA

1. The involvement of cGMP in vasodilatation produced by a range of nitrodilators was investigated using two different protein kinase G inhibitors, r_(p) 8-bromoguanosine-3′5′-cyclic monophosphothioate (RBrcGMPS) and KT5823. 2. The nitric oxide donors sodium nitroprusside (SNP), glyceryltrinitrate (GTN) and s-nitroso-acetylpenicillamine (SNAP), the endothelium-dependent vasodilator acetylcholine (ACh) as well as the cGMP analogues 8-(4-chlorophenylthio)-cGMP (CPTcGMP) and β-phenyl-1-N²-etheno-8-bromo-cGMP (PETcGMP) all relaxed rat aortic rings preconstricted with phenylephrine (0.1 μmol/L). 3. The protein kinase G inhibitor KT 5823 (10 μmol/L) produced a very small inhibition of the vasodilatation produced by GTN, but had no effect against vasodilatation produced by SNP, CPTcGMP or PETcGMP, which suggests that KT 5823 is not a useful tool in this system. 4. In contrast, RBrcGMPS (0.5 mmol/L) produced a rightward shift of the concentration-response curves to SNP, CPTcGMP and PETcGMP. RBrcGMPS (0.5 mmol/L) also completely abolished vasodilatation to ACh and GTN but, surprisingly, had no effect on vasodilatation produced by SNAP. 5. The guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 1 and 10 μmol/L) completely inhibited the relaxation produced by GTN, whereas SNAP still had an appreciable relaxant effect after ODQ (1 μmol/L). 6. The differential effect of RBrcGMPS and ODQ on the nitrodilators suggests that there are differences in the mechanism of dilatation between the nitrodilators.     

EFFECT OF PERINDOPRIL ON THE DEVELOPMENT OF ATHEROSCLEROSIS IN THE CHOLESTEROL-FED RABBIT

1. The aim of the study was to examine the effect of the angiotensin-converting enzyme inhibitor perindopril on the development of atheroma in the cholesterol-fed rabbit.
2. The normal human carotid artery, like most large human arteries, has a preformed diffuse intimal thickening. To model this thickening, the right carotid artery of the 12-week-old rabbit had an expanded balloon catheter passed down it to remove the endothelium and partially damage the media.
3. Fourteen weeks after this operation, a myointimal thickening similar in almost all respects to the human intimal thickening had developed. The rabbits were then divided into six groups of six rabbits fed on: (i) a 1% cholesterol diet; (ii) a 1% cholesterol diet plus a hypotensive dose of perindopril (0.3 mg/kg per day); (iii) a 1% cholesterol diet plus a non-hypotensive dose of perindopril (0.01 mg/kg per day); (iv) a normal diet; (v) a normal diet plus a hypotensive dose of perindopril (0.3 mg/kg per day); and (vi) a normal diet plus a non-hypotensive dose of perindopril (0.01 mg/kg per day).
4. After 6 weeks of treatment the animals were sacrificed. There were ameliorating effects of both hypotensive and non-hypotensive doses of perindopril on the development of plaques, as determined by the area of intima covered by Oil Red-O-staining plaque and light microscopy.
5. Cell culture studies indicated that perindopril has no effect on smooth muscle proliferation, but increases collagen and non-collagen synthesis by smooth muscle cells and decreases their binding of the atherogenic lipoprotein beta-very low density lipoprotein (β-VLDL).
6. The results suggest that perindopril has a beneficial effect in decreasing the severity of atherosclerotic lesions in the cholesterol-fed rabbit, possibly by affecting lipoprotein metabolism.     

胍丁胺对NMDA受体药理作用的研究进展

胍丁胺是一种新的神经递质和/或神经调质,是咪唑啉受体的内源性配体。它作为一种阳离子胺类物质,除了咪唑啉受体外,在生物体内还存在多个作用靶点,NMDA受体是其中最重要的作用靶点之一。本文就胍丁胺与NMDA受体在中枢神经系统的分布、胍丁胺在NMDA受体上的作用位点以及胍丁胺通过NMDA受体介导的药理作用等几个方面进行了综述。     

异紫堇定对兔输卵管平滑肌活动的影响

以住的研究表明,异紫堇定(isocorydine)有钙拮抗剂样作用。输卵管平滑肌的收缩活动是卵子运行的推动力之一,受多种因素的控制,并与细胞内游离钙浓度有关。本实验观察了异紫堇定对兔输卵管平滑肌机械活动及对卵运动的影响,并初步分析其作用机制。     

THE STUDY OF TACHYKININ RECEPTORS

1. Three high affinity receptors (NK1, NK2 and NK3) recognizing the C-terminal end of tachykinins have been described, with probable endogenous ligands substance P (SP-), neurokinin A and neurokinin B, respectively. 2. Other receptors recognizing the N-terminal regions of SP exist in adrenal medulla and central nervous system (CNS) with a low affinity receptor on mast cells. 3. NK1 receptors are associated with blood vessels, all types of smooth muscle, enteric ganglia and glands. NK2 receptors are found on gastrointestinal and urinary smooth muscle, but few peripheral NK3 receptors have been described. In contrast, NK1, NK3 but not NK2 receptors are widely distributed in the CNS. 4. Problems associated with the study of tachykinin receptors include low selectivity of endogenous tachykinins, poor antagonists and susceptibility of peptides to enzymatic degradation.