SHR大鼠延髓腹外侧头端区血管紧张素Ⅱ的作用研究

探讨ＳＨＲ及ＷＫＹ大鼠延髓腹外侧头端区（ｒｏｓｔｒａｌｖｅｎｔｒｏｌａｔｅｒａｌｍ ｅｄｕｌｌａ， ＲＶＬＭ）内微量注射血管紧张素Ⅱ（Ａｎｇ Ⅱ）和血管紧张素Ⅱ受体阻滞剂［Ｓａｒ１，Ｔｈｒ８］Ａｎｇ Ⅱ对心血管活动的影响。在ＳＨＲ及ＷＫＹ 大鼠，ＲＶＬＭ 微量注射人工脑脊液，不引起明显的心血管效应。ＲＶＬＭ 内微量注射递增剂量的Ａｎｇ Ⅱ（ｐｍ ｏｌ：０１，１０，１０，１００），引起血压升高，心率增加。两组实验动物血压、心率的变化无统计学差别。Ａｎｇ Ⅱ的效应可被预先注射［Ｓａｒ１，Ｔｈｒ８］Ａｎｇ Ⅱ所阻断。相反，ＲＶＬＭ 微量注射剂量递增的［Ｓａｒ１，Ｔｈｒ８］Ａｎｇ Ⅱ（ｐｍ ｏｌ：０１，１０，１０，１００），引起血压下降，心率减慢。在ＳＨＲ大鼠，血压下降的幅度明显大于ＷＫＹ大鼠，而心率的变化在两组动物中无显著差别。实验结果提示大鼠ＲＶＬＭ 内Ａｎｇ Ⅱ具有升高血压和增加心率的作用。Ａｎｇ Ⅱ的作用与Ａｎｇ Ⅱ受体介导有关。ＳＨＲ大鼠ＲＶＬＭ 内神经元对内源性Ａｎｇ Ⅱ的敏感性增高。ＳＨＲ大鼠高血压的形成与ＲＶＬＭ 内Ａｎｇ Ⅱ的升压作用增强有关。     

帕金森病和多系统萎缩患者脑脊液阿片肽含量变化的研究

采用放射免疫法检测８例帕金森病（ＰＤ）和１３例具帕金森综合征的多系统萎缩（ＭＳＤ）患者脑脊液（ＣＳＦ）中β－内啡肽（β－ＥＰ）、亮脑啡肽（ＬＥＫ）、强啡肽Ａ_（１－１３）（ＤｙｎＡ_（１－１３））含量。发现患者组ＣＳＦ中β－ＥＰ和ＬＥＫ含量显著高于对照组，ＤｙｎＡ_（１－１３）含量变化不显著。帕金森病和多系统萎缩两组间ＣＳＦ中三种阿片肽含量相差不明显。提示且ＥＰ、ＬＥＫ含量增高可能与ＰＤ和ＭＳＤ患者所共有的肌张力增高和肌强直等锥体外系症状产生有关。     

阿片机制参与基底外侧杏仁核的睡眠调节作用

应用多道睡眠描记术（ＰＳＧ）研究大鼠基底外侧杏仁核（ＢＬＮ）在睡眠－觉醒调节中的作用与机制。双侧ＢＬＮ 内微量注射损毁神经元胞体剂量的海人酸（ＫＡ）立即引起不眠状态,自第３ 天开始慢波睡眠（ＳＷＳ）增多,但快波睡眠（ＰＳ）不受影响。单侧ＢＬＮ内注射吗啡引起慢波睡眠抑制效应,而阿片受体阻断剂纳洛酮促进ＳＷＳ并可阻断吗啡的效应。环磷酸腺苷（ｃＡＭＰ）增加ＳＷＳ,但环磷酸鸟苷（ｃＧＭＰ）减少ＳＷＳ。鸟苷酸环化酶抑制剂亚甲蓝的效应与ｃＧＭＰ相反。本研究表明ＢＬＮ内阿片机制在睡眠－觉醒调节中具有重要作用,内源性阿片样物质抑制ＳＷＳ,这一作用可能是通过ｃＧＭＰ增多或ｃＡＭＰ减少实现的。     

氯沙坦对自发性高血压大鼠肾素—血管紧张素II水平的影响

目的：运动物验观察氯沙坦对自发性高血压大鼠（ＳＨＲ）血浆、下丘脑肾活性（ＲＡ）和血管紧张素ＩＩ（ＡｎｇＩＩ）水平的影响。方法：１６只雄性６周龄ＳＨＲ随机分为氯沙坦治疗组（ＳＨＲ＋Ｌ）和对照组（ＳＨＲ），另以８只同龄雄性Ｗｉｓｔａｒ－Ｋｙｏｔｏ大和为正常对照组（ＷＫＹ），氯沙坦组按３０ｍｇ．ｋｇ＾－１，氯沙坦组按３０ｍｇ．ｋｇ＾－１．ｄ＾－１约药，用药１８周后采用放免法检测血浆和下丘脑中ＲＡ和Ａｎｇ     

生长抑素调节疑核神经元兴奋性氨基酸受体介导的兴奋

在含有孤束核中央亚核（ＮＴＳｃ）疑核神经元密集区（ＡＭＢｃ）及孤束─疑核传导束的脑片，注射生长抑素（ＳＳＴ）于ＡＭＢｃ区，对Ｎ—ｍｅｔｈｙｌ—Ｄ－ａｓｐａｒｔａｔｅ（ＮＭＤＡ）引起的疑核神经元膜电位去极化有易化作用，而注射ｃｙｓｔｅａｍｉｎｅ耗竭内源性ＳＳＴ后，ＮＭＤＡ的去极化作用减弱；ＮＭＤＡ受体阻断剂Ｄ，Ｌ—２—ａｍｉｎｏ—７一ｐｂｏｓｐｈｏ－ｎｏｈｅｐｔａｎｏｉｃａｃｉｄ（ＡＰ─７）使疑核神经元兴奋性突触后电位（ＥＰＳＰ）幅度降低，而ＳＳＴ可翻转ＡＰ—７的抑制效应；对ｎｏｎ—ＮＭＤＡ介导的疑核神经元膜去极化，ｃｙｓｔｅａｍｉｎｅ亦对其有明显抑制作用；甘氨酸（ｇｌｙｃｉｎｅ）可阻断ＳＳＴ易化疑核神经元的去极化作用。这些结果表明，ＳＳＴ对疑核神经元兴富性氨基酸（ＥＡＡ）受体介导的兴奋起重要的调节作用。     

自发性高血压大鼠脑NOS亚型基因表达与SOD活性变化

目的 探讨自发性高血压大鼠（ＳＨＲ）中枢一氧化氨（ＮＯ）、超氧阴闻子改变及可能作用。方法 采用酶法及ＲＴ－ＰＣＲ等测定ＳＨＰ脑皮质超氧化物歧化酶（ＳＯＤ）、一氧化氮合酶（ＮＯＳ）活性及两种亚型（ｃＮＯＳ、ｉＮＯＳ）表达。结果 与对照组比较ＳＨＲ脑皮质ＳＯＤ活性显著增高（Ｐ〈０．０５）,ＮＯＳ活性无差异（Ｐ〉０．０５）,ｉＮＯＳ表达降低（Ｐ〈０．０１）,ｃＮＯＳ表达增高（Ｐ〈０．０５）。结论 ＮＯＳ     

生长抑素调节疑核神经兴奋性氨基酸受体介导的兴奋

在含有孤束中央亚核（ＮＴＳｃ）疑核神经元密集区（ＡＭＢｃ）及孤束－疑核传导束的脑片，注射生长抑素（ＳＳＴ）于ＡＭＢｃ区，对Ｎ－ｍｅｔｈｙｌ－Ｄ－ａｓｐａｒｔａｔｅ（ＮＭＤＡ）引起的疑核神经元膜电位去极化有易化作用，而注射ｃｙｓｔｅａｍｉｎｅ耗竭内源性ＳＳＴ后，ＮＭＤＡ的去极化作用减弱；ＮＭＤＡ受体阻断剂Ｄ，Ｌ－２－ａｍｉｎｏ－７－ｐｈｏｓｐｈｏｎｏｈｅｐｔａｎｏｉｃａｃｉｄ（ＡＰ－７）使疑核神经元     

Wilson病与微卫星DNA的连锁分析

目的探索国人Ｗｉｌｓｏｎ病（ＷＤ）基因位点（ＷＮＤ）与ＡＦＭ２３８ｖｃ３、Ｄ１３Ｓ３０１、Ｄ１３Ｓ３１６、Ｄ１３Ｓ２９６、及ＡＦＭ０８４ｘｃ５等５个微卫星ＤＮＡ（ＳＴＲ）之连锁关系，对ＷＮＤ进行精确定位。为ＷＤ基因克隆奠定基础。方法对２０个ＷＤ家系１１３名成员及１００名正常对照组成员的ＤＮＡ进行５个ＳＴＲ的聚合酶链反应（ＰＣＲ）扩增片段长度多态性分析；对ＷＮＤ及５个ＳＴＲ进行二点配对及多点连锁分析。结果ＷＮＤ与Ｄ１３Ｓ３０１、Ｄ１３Ｓ３１６、Ｄ１３Ｓ２９６呈紧密连锁，与ＡＦＭ２３８ｖｃ３及ＡＦＭ０８４ｘｃ５呈中度连锁。结论ＷＮＤ与５个ＳＴＲ的遗传连锁图谱为：着丝点—ＡＦＭ２３８ｖｃ３—Ｄ１３Ｓ３０１—ＷＮＤ—Ｄ１３Ｓ３１６—Ｄ１３Ｓ２９６—ＡＦＭ０８４ｘｃ５—端粒     

脑缺血对cNOS、iNOS基因表达的影响

一氧化氮（ＮＯ）由一氧化氮合酶（ＮＯＳ）专一催化合成。ＮＯＳ有两种生化型：原生型（ｃＮＯＳ）和诱生型（ｉＮＯＳ）,它们各具有特殊作用。我们在自发性高血压大鼠（ＳＨＲ）局灶脑缺血模型（ＭＣＡＯ）的基础上,采用ＲＴＰＣＲ技术,观察ｃＮＯＳ、ｉＮＯＳ的表...     

爱尔兰西部分裂症亚型的家庭研究

爱尔兰西部分裂症亚型的家庭研究【英】／ＫｅｎｄｌｅｒＫＳ……／／ＡｍＪＰｓｙｃｈｉａｔｒｙ—１９９４，１５１（６）：—８４９～８５６本文对精神分裂症的亚型进行了测查。精神分裂症诊断采用ＩＣＤ－９和ＤＳＭ－Ⅲ－Ｒ，就如下问题进行探讨：①用经典分型诊断精...     

Expression and localization of NK(1)R, substance P and CGRP are altered in dorsal root ganglia neurons of spontaneously hypertensive rats (SHR)

The kidneys play a pivotal role in the pathogenesis of essential hypertension because of a primary defect in renal hemodynamics and/or tubule hydro-saline handling that results in the retention of fluid and electrolytes. Previous studies have shown that increasing the renal pelvic pressure increased ipsilateral afferent renal nerve activity (ARNA), the ipsilateral renal pelvic release of substance P (SP) and the contralateral urinary sodium excretion in Wistar--Kyoto rats (WKy). However, spontaneously hypertensive rats (SHR) present an impaired renorenal reflex activity associated, partly, with a peripheral defect at the level of the sensory receptors in the renal pelvis. Furthermore, the renal pelvic administration of SP failed to increase ARNA in most of SHR at concentrations that produced marked increases in WKy. Since we have assessed the expression and localization of NK(1) receptor (NK(1)R), SP and calcitonin gene-related peptide (CGRP) in different dorsal root ganglia (DRG) cell subtypes and renal pelvis of 7- and 14-week-old SHR. The results of this study show increased SP and CGRP expression in the dorsal ganglia root cells of SHR compared to WKy rats. Additionally, there was a progressive, significant, age-dependent, decrease in NK(1)R expression on the membrane surface in SHR DRG cells and in the renal pelvis. In conclusion, the results of the present study suggest that the impaired activation of renal sensory neurons in SHR may be related to changes in the expression of neuropeptides and/or to a decreased presence of NK(1)R in DRG cells. Such abnormalities could contribute to the enhanced sodium retention and elevation of blood pressure seen in SHR.     

Identification of beta-adrenergic sensitive adenylate cyclase in rat thoracic duct

The effect of L-isoproterenol on the 3',5'-cyclic adenosine monophosphate (cAMP) generating system in rat thoracic duct membranes was investigated in order to identify beta-adrenergic receptors. L-Isoproterenol elicited a dose-dependent stimulation of cAMP formation; L-noradrenaline was less effective than L-isoproterenol in stimulating cAMP increase, whereas L-phenylephrine was without important effects on cAMP levels. L-Propranolol, a selective antagonist of beta-adrenergic receptors, caused a dose-dependent decrease of the effects of L-isoproterenol. In contrast, the L-isoproterenol-elicited increase of cAMP was unaffected by the alpha-adrenergic and dopamine receptor-blocking agents phentolamine and haloperidol. These data indicate that L-isoproterenol stimulates cAMP formation in the rat thoracic duct by a specific interaction with beta-adrenergic receptors positively coupled to adenylate cyclase.     

Expression of cyclooxygenase-2 mRNA in rat retrosplenial cortex following administration of phencyclidine

The effect of NMDA receptor antagonist phencyclidine (PCP) on expression of cyclooxygenase (COX)-2 mRNA in the rat brain was studied. Administration of PCP (12.5, 25 or 50 mg/kg, i.p., 6 h) caused marked induction of COX-2 mRNA and heat shock gene hsp-70 mRNA, a marker of neuronal injury, in the retrosplenial cortex, in a dose-dependent manner. These results suggest that COX-2 may play a role in the neurotoxicity of NMDA receptor antagonists.     

Blockade of long-term potentiation by phencyclidine and sigma opiates in the hippocampus in vivo and in vitro

Long-term potentiation (LTP) of synaptic transmission in the rat hippocampus in vivo and in vitro, was studied using field potentials. Pretreatment with phencyclidine (PCP) or 'sigma' opiates blocked LTP in vivo while mu and kappa opiates and the antagonist naloxone were ineffective. Scopolamine (20 mg/kg i.p.) neither prevented LTP nor antagonized the LTP-blocking effect of PCP. In vitro, PCP up to 100 microM did not alter synaptic activation of CA1 pyramidal cells by stratum radiatum stimulation but blocked LTP in a dose-dependent manner (ED50: 3 microM). The sigma opiate, cyclazocine, also prevented the induction of LTP in vitro while morphine and procaine were ineffective.     

Adenosine-mediated regulation of cyclic AMP levels in isolated incubated retinas

The effect of adenosine on the modulation of retinal cAMP levels was assessed in several mammalian species including mouse, rat, guinea pig and rabbit. Adenosine had no effect when added to incubated rat, mouse and guinea pig retinas. However, levels of cAMP were elevated in dose-dependent manner by adenosine in both light- and dark-adapted incubated rabbit retinas. Isobutylmethylxanthine (IBMX) blocked the elevation elicited by adenosine. Norepinephrine and dopamine also elevated cAMP in incubated rabbit retinas and these effects were not blocked by IBMX. The elevations of cyclic AMP levels produced by adenosine were additive with the effects of dopamine or norepinephrine. These results indicate that an adenosine-sensitive cAMP system exists in rabbit retina, and it is probably distinct from the dopamine and norepinephrine regulated cyclic AMP systems.     

Central catecholaminergic responses in hypoxic moderation of spontaneous hypertension

Exposure to hypobaric hypoxia (H; simulated altitude = 3658 m) was initiated in 5-week-old, male spontaneously hypertensive (SHR) and Wistar-Kyoto (WKy) normotensive rats while normoxic controls (N) for both groups were maintained under laboratory conditions. Significant attenuation of systolic arterial blood pressure was evident in SHR-H relative to SHR-N (125 +/- 6 vs. 145 +/- 5, mmHg; p less than 0.05) while blood pressure in the normotensive, Wistar-Kyoto rat was not affected by 20 days of exposure to hypoxia (WKy-H, 116 +/- 2 vs. WKy-N, 117 +/- 5, mmHg). Increased contents of norepinephrine and dopamine in brain stem, striatum, hypothalamus, and frontal cortex in SHR versus WKy indicated a possible involvement of central catecholaminergic mechanisms with spontaneous hypertension. Hypoxia significantly decreased neuronal contents of both neurotransmitters, typically on both days studied (days 4 and 21 of altitude treatment). In striatum and hypothalamus, dihydroxyphenylacetic acid to dopamine ratios indicated that dopamine turnover was decreased with hypoxia. Hypoxia elicits catecholaminergic responses consistent with profiles found following ICV administration of 6-hydroxydopamine, a sympatholytic agent that also prevents the development of spontaneous hypertension. Hypoxic mitigation of spontaneous hypertension may occur via mechanisms initiated at the level of the CNS.     

Cholinergic response of isolated rat atria to recombinant rat interferon-gamma

Addition of recombinant rat interferon-gamma (IFN-gamma) to beating rat atria decreased the contractile strength in a dose-dependent manner. The effect was specific of IFN-gamma since it was abrogated by monoclonal anti-rat IFN-gamma. It required the activation of the cholinergic system of the heart as inhibition of both nicotinic (10(-7) M hexametonium) and muscarinic cholinoceptors (10(-7) M atropine) prevented the reaction. Hemicholinium (2 x 10(-5) M) and tetrodotoxin (5 x 10(-7) M) also reduced the response. Likewise, IFN-gamma potentiated the action of the muscarinic agonist carbachol. IFN-gamma simulated the biological effect of cholinergic agonists because: (a) it increased cGMP formation; (b) it decreased cAMP formation; and (c) it reduced heart contractility at doses that can be considered physiologic. IFN-gamma also modified the muscarinic receptor by interfering with the binding of the radiolabelled antagonist quinuclidinyl benzilate [( 3H]QNB). It is suggested that IFN-gamma binding to IFN-gamma receptors in the heart may lead to a cholinergic response by interaction of both receptor systems on the surface of atrial cells.     

Increased expression of zif268 mRNA in rat retrosplenial cortex following administration of phencyclidine

Phencyclidine (PCP) has been shown to cause neurotoxicity in rat retrosplenial cortex following a single administration, although the precise mechanism underlying PCP-induced neurotoxicity is unclear. Using in situ hybridization and immunohistochemistry, we studied the effects of PCP on expression of immediate early gene zif268 mRNA and zif268 protein in the rat brain. High constitutive levels of zif268 mRNA and zif268 immunoreactivity were observed in the brain of control rats. Administration of PCP (12.5, 25 or 50 mg/kg, i.p., 6 h) caused marked induction of zif268 mRNA in the rat retrosplenial cortex, in a dose-dependent manner. However, the basal levels of zif268 mRNA in the other regions of cerebral cortex were decreased by administration of PCP. Emulsion-autoradiographical study suggested that marked expression of zif268 mRNA was observed in the layers III and IV of retrosplenial cortex where the neurotoxicity of PCP was detected. Furthermore, zif268 immunoreactivity in the layer IV of retrosplenial cortex was not changed by administration of PCP (25 mg/kg, i.p., 5 h), but that in the other layers of retrosplenial cortex was reduced by PCP. These results suggest that immediate early gene zif268 may, in part, play a role in the neurotoxicity of NMDA receptor antagonists such as PCP.     

Nicotinic acetylcholine receptor desensitization is regulated by activation-induced extracellular adenosine accumulation.

Adenosine modulation of nicotinic ACh receptor (nAChR) function was studied in primary cultures of rat skeletal muscle. Activation of the nAChR by carbachol increased extracellular adenosine concentration in a dose-dependent manner. Furthermore, carbachol activation of the nicotinic receptor resulted in a twofold increase in cAMP levels in the muscle cells. The carbachol-dependent increase in cAMP levels was inhibited by adenosine receptor antagonists as well as by nicotinic receptor antagonists. These results suggest that the increased cAMP levels were due to adenosine receptor activation by the extracellular adenosine accumulated on nAChR activation. Others have shown that desensitization of the nAChR by agonist is mediated, in part, by phosphorylation. Since we found that nicotinic cholinergic agonists also cause adenosine accumulation with concomitant cAMP increases, we determined whether the accumulated adenosine has a role in desensitization. We found that the adenosine receptor antagonist, BW1434U, significantly inhibited carbachol-induced nAChR desensitization, indicating that extracellular adenosine is involved in nAChR desensitization. Our data suggest that nAChR function is regulated via a feedback mechanism mediated by adenosine released from muscle on activation of the nAChR.     

Opposing effects by pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal peptide on hippocampal synaptic transmission

Pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), and their receptors have been localized within the hippocampus but their physiological function on synaptic transmission is still unclear. We investigated the effects of PACAP and VIP on evoked excitatory postsynaptic currents (EPSCs) recorded with patch clamp from CA1 pyramidal neurons in rat hippocampal slices. Bath application of PACAP reversibly reduced EPSC amplitude. This effect was partly prevented by intracellular addition of (R)-adenosine, cyclic 3',5'-hydrogenphosphorothioate (cAMPS-Rp), a cAMP antagonist inhibiting protein kinase A, but not by the calcium chelator 1,2-bis (2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Application of VIP induced a long-lasting increase of EPSC amplitude that was completely abolished when cAMPS-Rp was included in the intracellular solution. PACAP and VIP effects on EPSCs were mimicked by the cAMP agonist 8-bromoadenosine-3',5'-cyclic monophosphate (8-Br-cAMP). The differing abilities of PACAP and VIP to modulate transmission efficiency over long periods of time, through the cAMP/PKA pathway, suggest that these neuropeptides may exert opposing roles in synaptic plasticity.