Calcium and cyclic adenosine monophosphate as second messengers for vasopressin in the rat inner medullary collecting duct.

Vasopressin increases both the urea permeability and osmotic water permeability in the terminal part of the renal inner medullary collecting duct (terminal IMCD). To identify the second messengers that mediate these responses, we measured urea permeability, osmotic water permeability, intracellular calcium concentration, and cyclic AMP accumulation in isolated terminal IMCDs. After addition of vasopressin, a transient rise in intracellular calcium occurred that was coincident with increases in cyclic AMP accumulation and urea permeability. Half-maximal increases in urea permeability and osmotic water permeability occurred with 0.01 nM vasopressin. The threshold concentration for a measurable increase in cyclic AMP accumulation was approximately 0.01 nM, while measurable increases in intracellular calcium required much higher vasopressin concentrations (greater than 0.1 nM). Exogenous cyclic AMP (1 mM 8-Br-cAMP) mimicked the effect of vasopressin on urea permeability but did not produce a measurable change in intracellular calcium concentration. Conclusions: (a) Cyclic AMP is the second messenger that mediates the urea permeability response to vasopressin in the rat terminal IMCD. (b) Vasopressin increases the intracellular calcium concentration in the rat terminal IMCD, but the physiological role of this response is not yet known.     

Effect of the carboxyl-terminal tripeptide of vasopressin on plasma free fatty acids and cyclic adenosine monophosphate in man.

The carboxyl-terminal tripeptide of casopressin (Pro-Arg-Gly.NH2) and adrenocorticotrophic hormone (ACTH) were injected intravenously into six human subjects, and the effects of these peptides on plasma free fatty acids (FFA) and cAMP concentrations were compared with that of saline. Twenty mug of the tripetide and 100 mug of ACTH INCREASED THE PLASMA FFA CONCENTRATION TO THE SAME EXTENT, WHEREAS 200 MUG OF THE TRIPETIDE WAS WITHOUT THIS LIPOLYTIC EFFECT. ACTH and the smaller dose of the tripeptide elevated the plasma cAMP level only in the same two subjects.     

复方丹参滴丸干预短暂性脑缺血发作时对血浆环磷酸腺苷和环磷酸鸟苷的影响

背景：在缺血性脑卒中急性期和恢复期皆可见血小板处于活化状态，环磷酸腺苷和环磷酸鸟苷与血小板功能密切相关。目的：观察复方丹参滴丸预防治疗短暂性脑缺血发作的临床疗效及对血浆环磷酸腺苷、环磷酸鸟苷的影响。设计：随机对照实验。单位：滨州医学院附属医院神经科。对象：选择2000-09／2001—04滨州医学院附属医院神经科门诊180例自愿参加本实验的短暂性脑缺血发作患者。采用随机数字表将患者按给予复方丹参滴丸剂量大小分为3组。给药10粒／d组60例，男35例，女25例；年龄50～70岁，平均（54．3&;#177;7．2）岁；给药20粒／d组60例，男32例，女28例；年龄49～62岁，平均（55．7&;#177;5．1）岁。给药30粒／d组60例，男33例，女27例；年龄52&;#177;69岁，平均（54．9&;#177;5．5）岁。方法：给药10粒／d组，1次／d，10粒／次；给药20粒／d组，2次／d，10粒／次；给药30粒／d组，3次／d，10粒／次。患者均在服药4周后，晨抽血3mL，采用放射免疫分析法，测定三组血浆中的环磷酸腺苷、环磷酸尿苷含量。每例患者均3个月随访一次，共随访18个月：①观察短暂性脑缺血发作的发作次数及发作形式。②发生缺血性脑卒中例数（包括心、脑卒中）。（④副作用：消化道反应，牙龈出血、鼻出血、皮下出血、口麻、头痛、头晕等。主要观察指标：①各组患者短暂性脑缺血发作的发作形式。②各组患者发生缺血性脑卒中例数。③各组患者副作用发生情况。④各组患者血浆中环磷酸腺苷，环磷酸鸟苷水平。结果：180例患者均进入结果分析。①发生短暂性脑缺血发作的发作例数：给药10粒／d组，发生颈内动脉系统短暂性脑缺血发作的1例；发生椎动脉系统短暂性脑缺血发作的2例；发生脑梗死的1例；发生心肌梗死的2例；给药20粒／d组，分别为2，2，1例；给药30粒／d组．分别为1，2，1例。②发生缺血性脑卒中例数：3组分别发生脑卒中的例数为6．5，4例。⑨各组患者副作用发生情况：三组不良事件及副反应分别为1．2，4例，其中给药10粒／d组出现口周麻木1例，给药20粒／d组出现口周麻木和头痛各1例，给药30粒／d组出现胃肠道反应1例，口周麻木2例，头晕1例；末出现牙龈出血、鼻出血及皮下出血病例，同时患者亦未因上述副作用退出治疗。各组比较，无显著性差异（P〉0．05）。（少各组患者血浆中环磷酸腺苷，环磷酸鸟背水平：3组环磷酸腺苷分别为（21．22&;#177;3．94），（22．5&;#177;3．67），（23．1&;#177;7．7）ng/L；环磷酸鸟苷分别为（3．67&;#177;1．18）．（4．74&;#177;2．12）．（4．6&;#177;0．7）ng／L，（P〉0．05）．结论：复方丹参滴丸在短暂性脑缺血发作的二级预防中，有肯定的疗效，各剂量比较疗效基本一致，同时无明显副作用。     

复方丹参滴丸干预短暂性脑缺血发作时对血浆环磷酸腺苷和环磷酸鸟苷的影响

背景在缺血性脑卒中急性期和恢复期皆可见血小板处于活化状态,环磷酸腺苷和环磷酸鸟苷与血小板功能密切相关.目的观察复方丹参滴丸预防治疗短暂性脑缺血发作的临床疗效及对血浆环磷酸腺苷、环磷酸鸟苷的影响.设计随机对照实验.单位滨州医学院附属医院神经科.对象选择2000-09/2001-04滨州医学院附属医院神经科门诊180例自愿参加本实验的短暂性脑缺血发作患者.采用随机数字表将患者按给予复方丹参滴丸剂量大小分为3组.给药10粒/d组60例,男35例,女25例;年龄50～70岁,平均(54.3±7.2)岁;给药20粒/d组60例,男32例,女28例;年龄49～62岁,平均(55.7±5.1)岁.给药30粒/d组60例,男33例,女27例;年龄52～69岁,平均(54.9±5.5)岁.方法给药10粒/d组,1次/d,10粒/次;给药20粒/d组,2次/d,10粒/次;给药30粒/d组,3次/d,10粒/次.患者均在服药4周后,晨抽血3mL,采用放射免疫分析法,测定三组血浆中的环磷酸腺苷、环磷酸尿苷含量.每例患者均3个月随访一次,共随访18个月①观察短暂性脑缺血发作的发作次数及发作形式.②发生缺血性脑卒中例数(包括心、脑卒中).③副作用消化道反应,牙龈出血、鼻出血、皮下出血、口麻、头痛、头晕等.主要观察指标①各组患者短暂性脑缺血发作的发作形式.②各组患者发生缺血性脑卒中例数.③各组患者副作用发生情况.④各组患者血浆中环磷酸腺苷,环磷酸鸟苷水平.结果180例患者均进入结果分析.①发生短暂性脑缺血发作的发作例数给药10粒/d组,发生颈内动脉系统短暂性脑缺血发作的1例;发生椎动脉系统短暂性脑缺血发作的2例;发生脑梗死的1例;发生心肌梗死的2例;给药20粒/d组,分别为2,2,1例;给药30粒/d组,分别为1,2,1例.②发生缺血性脑卒中例数3组分别发生脑卒中的例数为6,5,4例.③各组患者副作用发生情况三组不良事件及副反应分别为1,2,4例,其中给药10粒/d组出现口周麻木1例,给药20粒/d组出现口周麻木和头痛各1例,给药30粒/d组出现胃肠道反应1例,口周麻木2例,头晕1例;未出现牙龈出血、鼻出血及皮下出血病例,同时患者亦未因上述副作用退出治疗.各组比较,无显著性差异(P＞0.05).④各组患者血浆中环磷酸腺苷,环磷酸鸟苷水平3组环磷酸腺苷分别为(2122±3.94),(22.5±3.67),(23.1±7.7)ng/L;环磷酸鸟苷分别为(3.67±1.18),(4.74±2.12),(4.6±0.7)ng/L,(P＞0.05).结论复方丹参滴丸在短暂性脑缺血发作的二级预防中,有肯定的疗效,各剂量比较疗效基本一致,同时无明显副作用.     

Effects of atrial natriuretic factor on cyclic guanosine monophosphate and cyclic adenosine monophosphate accumulation in microdissected nephron segments from rats.

Atrial natriuretic factor (ANF) (1 microM) markedly increased cyclic guanosine monophosphate (cGMP) content in microdissected glomeruli (35-fold) and in microdissected inner medullary collecting ducts (IMCD) (20-fold). ANF caused little or no increase in cGMP content in other nephron segments. The threshold concentration for increased cGMP accumulation by ANF was 0.1-1 nM in IMCD, which is in the range reported for rat plasma. Sodium nitroprusside (1 mM), which selectively stimulates soluble guanylate cyclase, increased cGMP content in glomeruli but not in IMCD. ANF did not alter cAMP accumulation in the absence or presence of vasopressin (AVP) or parathyroid hormone (PTH) in outer and inner medullary tubule suspensions, or in microdissected proximal convoluted tubules (PCT), medullary thick ascending limbs (MAL) or IMCD. These data are compatible with the hypothesis that cGMP is a second messenger for a physiologic action of ANF in the inner medullary collecting duct. ANF apparently activates membrane-bound guanylate cyclase in this segment.     

学习记忆过程中磷酸化的环磷酸腺苷反应单元结合蛋白在大鼠脑纹状体内的表达

背景：脑纹状体边缘区是在大鼠脑纹状体发现的一个新亚区，已证明边缘区与脑的学习记忆功能密切相关。而且，即刻早期基因c-fos，c-jun涉及边缘区内学习记忆的信号转导过程。但边缘区在参与学习记忆过程中还启动了其他哪些中间环节？环磷酸腺苷反应单元结合蛋白是长期记忆形成过程所必需的一种关键分子。检测磷酸化的环磷酸腺苷反应单元结合蛋白在纹状体是否有表达及其分布情况，有助于从分子水平探索学习记忆过程中纹状体的信号转导机制问题。目的：探讨大鼠在学习记忆过程中磷酸化环磷酸腺苷反应单元结合蛋白在脑纹状体内的表达情况。设计：完全随机对照。单位：第一军医大学珠江医院神经科学研究所。材料：实验于2003-04/08在第一军医大学珠江医院神经科学研究所完成。选择第一军医大学实验动物中心提供的健康雄性成年SD大鼠48只，经两次Y型迷宫（MG-2型，三兴声电公司）实验筛选后获得合格动物40只。方法：40只合格动物随机分成4组：训练组10只大鼠在Y迷宫中接受厌暗逃避反射训练；假训练灯光刺激组10只大鼠进入Y迷宫后仅接受灯光刺激，迷宫底部电网无电流通过；假训练电网刺激组10只大鼠进入Y迷宫后，则在无灯光刺激的情况下仅接受迷宫底部的电网刺激；对照组10只大鼠被单纯置于无光无电的Y迷宫环境中。动物在Y迷宫中进行学习记忆训练后，应用免疫组织化学方法检测磷酸化的环磷酸腺苷反应单元结合蛋白在脑纹状体内的表达。主要观察指标：磷酸化的环磷酸腺苷反应单元结合蛋白在脑纹状体内的表达。结果：40只实验大鼠均进入结果分析。①训练组大鼠经电Y迷宫训练后，脑纹状体内侧的边缘区内即有明显的磷酸化的环磷酸腺苷反应单元结合蛋白阳性表达，而假训练组或对照组的边缘区内均无明显的磷酸化的环磷酸腺苷反应单元结合蛋白阳性表达。②在海马、前额叶皮质和扣带回等处也有较多的磷酸化的环磷酸腺苷反应单元结合蛋白阳性表达。结论：大鼠进行电Y迷宫厌暗学习时，脑纹状体边缘区内的转录因子磷酸化的环磷酸腺苷反应单元结合蛋白参与学习记忆的信号转导过程。     

学习记忆过程中磷酸化的环磷酸腺苷反应单元结合蛋白在大鼠脑纹状体内的表达

背景脑纹状体边缘区是在大鼠脑纹状体发现的一个新亚区,已证明边缘区与脑的学习记忆功能密切相关.而且,即刻早期基因c-fos,c-jun涉及边缘区内学习记忆的信号转导过程.但边缘区在参与学习记忆过程中还启动了其他哪些中间环节?环磷酸腺苷反应单元结合蛋白是长期记忆形成过程所必需的一种关键分子.检测磷酸化的环磷酸腺苷反应单元结合蛋白在纹状体是否有表达及其分布情况,有助于从分子水平探索学习记忆过程中纹状体的信号转导机制问题.目的探讨大鼠在学习记忆过程中磷酸化环磷酸腺苷反应单元结合蛋白在脑纹状体内的表达情况.设计完全随机对照.单位第一军医大学珠江医院神经科学研究所.材料实验于2003-04/08在第一军医大学珠江医院神经科学研究所完成.选择第一军医大学实验动物中心提供的健康雄性成年SD大鼠48只,经两次Y型迷宫(MG-2型,三兴声电公司)实验筛选后获得合格动物40只.方法40只合格动物随机分成4组训练组10只大鼠在Y迷宫中接受厌暗逃避反射训练;假训练灯光刺激组10只大鼠进入Y迷宫后仅接受灯光刺激,迷宫底部电网无电流通过;假训练电网刺激组10只大鼠进入Y迷宫后,则在无灯光刺激的情况下仅接受迷宫底部的电网刺激;对照组10只大鼠被单纯置于无光无电的Y迷宫环境中.动物在Y迷宫中进行学习记忆训练后,应用免疫组织化学方法检测磷酸化的环磷酸腺苷反应单元结合蛋白在脑纹状体内的表达.主要观察指标磷酸化的环磷酸腺苷反应单元结合蛋白在脑纹状体内的表达.结果40只实验大鼠均进入结果分析.①训练组大鼠经电Y迷宫训练后,脑纹状体内侧的边缘区内即有明显的磷酸化的环磷酸腺苷反应单元结合蛋白阳性表达,而假训练组或对照组的边缘区内均无明显的磷酸化的环磷酸腺苷反应单元结合蛋白阳性表达.②在海马、前额叶皮质和扣带回等处也有较多的磷酸化的环磷酸腺苷反应单元结合蛋白阳性表达.结论大鼠进行电Y迷宫厌暗学习时,脑纹状体边缘区内的转录因子磷酸化的环磷酸腺苷反应单元结合蛋白参与学习记忆的信号转导过程.     

黄蒲通窍胶囊对血管性痴呆大鼠血浆及脑组织环磷腺苷酸、环磷酸鸟苷和一氧化氮的影响

目的:观察中药黄蒲通窍胶囊对血管性痴呆大鼠血浆及脑组织环磷腺苷酸、环磷酸鸟苷和一氧化氮变化的影响。方法:实验于2004-05在安徽中医学院第一附属医院实验中心进行。选用雄性Wistar大鼠100只,分为空白组15只;假手术组15只;余下70只全部造模,随机选取造模成功大鼠45只,分成模型组、黄蒲通窍组、阿米三嗪3组各15只。空白组不干预,假手术组不阻断大脑中动脉,其他3组线栓法制作大脑中动脉栓塞所致的血管性痴呆大鼠模型。黄蒲通窍组和阿米三嗪组按照大鼠体质量以0.01mL/g的剂量灌胃给药,其他3组予以蒸馏水(0.01mL/g)灌胃,于造模结束第2天开始给药,1次/d,连续处理28d。观察各组大鼠血浆及脑组织环磷腺苷酸、环磷酸鸟苷和一氧化氮的变化。结果:58只大鼠进入结果分析。①环磷腺苷酸:模型组大鼠血浆和脑组织中的环磷腺苷酸浓度降低犤(0.34±0.11),(17.07±2.81)nmol/L犦,黄蒲通窍组、阿米三嗪组较模型组明显升高犤(0.96±0.11),(28.61±6.98),(1.08±0.13),(32.10±6.41)nmol/L犦。②环磷酸鸟苷:模型组大鼠血浆和脑组织中的环磷酸鸟苷浓度升高犤(0.26±0.05),(5.92±1.15)nmol/L犦,黄蒲通窍组、阿米三嗪组较模型组明显降低犤(0.14±0.05),(4.08±0.30),(0.14±0.05),(3.74±0.25)nmol/L犦。③模型组一氧化氮浓     

Virus-induced alterations in cyclic adenosine monophosphate generation in hamster islets of Langerhans.

Inoculation of golden Syrian hamsters with Venezuelan encephalitis (VE) virus results in a sustained diminution in glucose-stimulated insulin release that is correctable by cyclic (c) AMP analogs and phosphodiesterase inhibitors. This suggested the importance of directly measuring cAMP content in VE-infected and control islets in response to insulin secretagogues. The basal cAMP content of VE-infected islets (0.14 +/- 0.02 pmol/micrograms islet DNA) was approximately half that of control islets (0.27 +/- 0.02 pmol/micrograms islet DNA) (P less than 0.05). In the presence of 10 microM glucagon (and 3 mM glucose), the rate of cAMP generation in VE-infected islets was only half that of control islets. With 10 mM alpha-ketoisocaproic acid, the rates of cAMP generation were indistinguishable between control and experimental groups. In response to 20 mM glucose and 3-isobutyl-1-methylxanthine (IBMX) (a phosphodiesterase inhibitor), cAMP generation in VE-infected islets was 81% (NS) of the control rate. When a more specific phosphodiesterase inhibitor, RO 20-1724, was used with 20 mM glucose, cAMP generation in the infected islets was only 44% (P less than 0.001) of the control value. Insulin secretion over the perifusion period paralleled the cAMP levels. In the presence of 10 mM alpha-ketoisocaproic acid, there was no difference in insulin secretion between VE-infected and control islets, while there was a statistically significant (P less than 0.05) difference with 10 microM glucagon or 20 mM glucose (in 1 mM RO 20-1724). These data point to a defect in the cAMP generation system of VE-infected islets, although additional factors involved in insulin secretion may also be impaired by the virus.     

Leukocyte cyclic adenosine monophosphate in asthmatic children. Effects of adrenergic therapy.

Blood specimens for measurement of leukocyte cyclic adenosine monophosphate (AMP) were obtained at weekly intervals from asthmatic children who were participating in a double-blind, crossover study to compare the effects of two adrenergic agents and a placebo. When patients were treated with the placebo, the basal measurements and the cyclic AMP responses of leukocytes to in vitro stimulation with epinephrine (10(-4) M) were similar to those of normal subjects but within one week after initiation of treatment with an adrenergic bronchodilator, leukocyte cyclic AMP responses to adrenergic stimulation in vitro decreased and remained low during the remainder of the treatment period. Within one week after discontinuation of adrenergic therapy, leukocyte cyclic AMP responses returned to the control level. Our results indicate that the alterations in leukocyte cyclic AMP metabolism which have been observed previously in asthmatic patients may result from medications used for treatment of asthma.     

衰老对大鼠阴茎组织中一氧化氮,cGMP,cAMP的影响及与勃起功能障碍的关系

目的:观察衰老对一氧化氮NO,cAMP,cGMP含量变化,探讨其与阴()茎勃起功能障碍的关系。方法:应用亚硝酸还原酶法及放免法对不同月龄,8,16,24个月)大(2鼠阴茎组织中NO及cGMP,cAMP含量分别进行检测。结果:随月龄增加,NO含量先增高,再降低,其中月龄最高,24月龄8最低,各月龄组间差异有非常显著性意义(P<0.001);cGMP,cAMP含量均随月龄增加而逐渐下降,各月龄组间差异也有非常显著性意义(P<0.001)。结论:衰老对NO及cGMP,cAMP有显著影响,提示临床应用增加NO,cGMP,cAMP的药物对勃起功能障碍的康复有重要价值。     

Pharmacological characterization of rat renal medulla dopamine-sensitive cyclic adenosine monophosphate generating system

The dopamine (DA) DA-1 and DA-2 receptors coupled to 3'-5'-cyclic adenosine monophosphate (cAMP) generating system were characterized in membrane particles of the rat kidney medulla. In confirmation of reports using central and other peripheral tissues, activation of DA-1 receptors with DA, apomorphine or SKF 82526 induced accumulation of cAMP. This effect was blocked by the DA-1 receptors antagonist SCH 23390 and by the other DA-2 receptor antagonists fluphenazine and haloperidol. DA-2 receptor responses coupled negatively to the cAMP generating system were obtained by incubating renal medulla membrane particles with DA or SKF 82526 together with SCH 23390. DA-2 receptor responses were also elicited with the receptor agonists quinpirole and bromocriptine in the absence of SCH 23390. These inhibitory effects on cAMP generation were abolished by the DA-2 receptor antagonist l-sulpiride. Our findings suggest that rat renal medulla contains DA DA-1 and DA-2 receptors similar to those found in brain and in other peripheral tissues. The physiological significance of these receptors, if any, should be established in future studies.     

Natriuretic peptides maintain sodium homoeostasis during chronic volume loading post-myocardial infarction in sheep

The impaired ability to excrete sodium is a key feature of established congestive heart failure and is also apparent in asymptomatic left ventricular (LV) impairment. However, few studies have examined responses to chronic volume loading immediately post-myocardial infarction (MI). Experimental MI was induced in six sheep by thrombogenic coil coronary artery occlusion, and resulted in significant LV dysfunction with reduced LV ejection fraction ( P =0.001) and subsequent remodelling (increased LV volumes, P =0.015). Chronic volume loading with 2, 3 and 4 litres/day intravenous saline (each for 7 days) showed no evidence of renal sodium or volume retention in sheep with experimental MI compared with six normal control sheep. Plasma levels of brain natriuretic peptide (BNP), N-terminal pro-BNP and cGMP (all P <0.05) were higher in the MI group compared with normal control sheep. There were no differences in haemodynamics, body mass or renin-aldosterone levels between groups. This study provides evidence that natriuretic peptides play a pivotal role in preserving volume/electrolyte balance in the early stages of post-MI cardiac dysfunction.