GABA-receptor stimulation enhances norepinephrine-induced polyphosphoinositide metabolism in rat hippocampal slices

The effect of gamma-aminobutyric acid (GABA)receptor stimulation on norepinephrine (NE)-induced metabolism of polyphosphoinositides (PIPs) was studied in rat hippocampal slices. Inositol phosphates (IPs), PIPs, and phosphatidic acid were measured. NE induced formation of IPs and phosphatidic acid in a dose-dependent manner with an EC50 of 4.5 microM. GABA, 3-aminopropanesulphonic acid (3APS) and muscimol did not affect PIPs breakdown, but they strongly increased (greater than 100%) PIPs metabolism induced by 1 microM NE. Their action was antagonized by bicuculline (10 microM). We discuss the implications of these findings in hippocampal neurotransmission.     

远端保护装置对急性心肌梗死患者神经内分泌的影响

目的 探讨急性ST段抬高性心肌梗死(STEMI)急诊经皮冠状动脉成形术(PCI)中应用远端保护装置对神经内分泌指标的影响及其临床价值.方法 本研究为前瞻性对照研究,将2004年9月至2006年12月在青岛市市立医院行急诊PCI的72例STEMI患者随机(随机数字法)分为远端保护组(GW)和非远端保护组(NGW).入选标准:发病在6 h之内,胸痛持续≥30 min且用硝酸甘油不缓解;在12导联心电图上至少有2个相邻导联ST-段抬高≥0.2 mV;梗死相关血管(IRA)近段或中段直径≥3 mm;血浆中的肌酸激酶增高.排除标准为:血流动力学状态不稳定者;严重心功能不全;多支血管病变拟行冠状动脉搭桥者;左主干病变;急性心肌梗死机械并发症.于术前、术后1 d,2 d,3 d,5 d分别测定外周血中内皮素(ET)、血浆肾索活性(PRA)、醛固酮(ALD)、血管紧张素Ⅱ(Ang Ⅱ)、去甲肾上腺素(NE)、肾上腺素(E)水平.分别对术后1,2,3,5 d的ET,PRA,ALD,AngⅡ,NE,E等数值应用成组t检验进行两组间的比较.结果 两组病例均成功植入支架,术前两组患者的神经内分泌因子水平差异无统计学意义(P＜0.05).GW组较NGW组ET,PRA,ALD,AngⅡ,NE,E等神经内分泌因子水平于术后第1天下降明显,两组差异具有统计学意义(P＜0.05).结论 急性心肌梗死急诊PCI手术中应用远端保护装置可以使神经内分泌指标降低,减少其不利影响,促进心肌的恢复.     

Early effects of experimental diabetes on central catecholamine concentrations

Six days after induction of diabetes norepinephrine (NE), 3,4-dihydroxyphenylalanine and dopamine concentrations were determined in spinal cord, cerebellum, pons/medulla oblongata and the remaining brain of diabetic rats. Only cerebellar NE levels were significantly increased by 21% compared to age-matched controls. This effect was not seen when diabetic rats received insulin replacement therapy. Fifty-two days after induction of diabetes cerebellar NE levels in diabetic rats were further increased (+37%), implying an enduring and progressive effect. The data show that even with a short period of uncontrolled diabetes central neurochemical alterations occur.     

Monoamines in the caudal neurosecretory complex: Biochemistry and immunohistochemistry

Monoaminergic inputs to the caudal neurosecretory complex (CNc) of Poecilia latipinna have been identified using histofluorescence and immunohistochemical techniques. The present study was undertaken to identify specific monoamines and determine the relative contribution of indolamines and catecholamines in supraspinal and intrinsic innervation of the nucleus. The CNc was deafferented by transecting the spinal cord rostral to the CNc. Ten days subsequently, CNc of spinal-transected and control fish were processed for either biochemical or immunohistochemical analysis. Norepinephrine and serotonin were detected in pooled samples of control CNc. Following deafferentation, the content of both monoamines was diminished. Using immunohistochemical labeling for serotonin or for the catecholamine-synthesizing enzymes, tyrosine hydroxylase (TH) or dopamine-beta-hydroxylase (DBH), the number of monoamine fibers was decreased in deafferented CNc compared to control. A substantial serotonergic innervation remains after deafferentation, as evidenced by serotonin-positive neurons and heavy, varicose fibers. Occasional TH/DBH-positive cells and fibers remain after deafferentation. These data suggest that both norepinephrine and serotonin are associated with descending supraspinal projections, while serotonin predominates as the intrinsic monoamine.     

1型多聚二磷酸腺苷核糖合成酶对去甲肾上腺素诱导心脏成纤维细胞表达基质金属蛋白酶的影响

目的:探讨1型多聚二磷酸腺苷核糖合成酶(PARP-1)对去甲肾上腺素(NE)诱导培养的大鼠心脏成纤维细胞基质金属蛋白酶(MMP)-1,MMP-9及金属蛋白酶组织抑制剂(TIMP)-1表达的调节作用及其机制。方法:①培养乳鼠心脏成纤维细胞,10μmol/LNE刺激细胞24h,使用实时定量PCR法检测MMP-1、MMP-9及TIMP-1的基因表达水平;使用PARP抑制剂3-氨基苯甲酰胺(3-aminobenzamide,3AB)后,观察PARP-1对上述基因表达的影响。②检测心脏成纤维细胞内活性氧(ROS)水平、PARP酶活性的变化。③采用凝胶阻滞实验检测心脏成纤维细胞内转录因子AP-1的DNA结合能力,研究PARP-1对AP-1DNA结合能力的影响。结果:NE诱导心脏成纤维细胞内MMP-1,MMP-9及TIMP-1的基因表达水平明显增加。细胞内ROS产生增加,PARP酶被激活。核内转录因子AP-1的DNA结合能力明显增强。PARP抑制剂3AB可明显减少NE诱导的MMP-1、MMP-9及TIMP-1的基因表达水平,同时显著抑制AP-1的DNA结合能力。使用抗氧化剂vitC减少ROS产生,抑制了NE诱导的PARP-1活性增加及AP-1的DNA结合,进而显著降低了NE诱导的MMP-1、MMP-9及TIMP-1的基因表达水平。结论:NE刺激心脏成纤维细胞内ROS产生明显增多,大量的ROS激活了PARP使其酶活性显著增高,PARP通过调节转录因子AP-1的DNA结合调控了MMP-1,MMP-9及TIMP-1的基因表达。PARP可能是心脏纤维化过程中的重要调节机制之一。     

Sympathetic activation and inflammatory response in patients with subarachnoid haemorrhage

Objective The aim of this study was to evaluate the correlation between sympathetic nervous activation and the immune response in patients following subarachnoid haemorrhage (SAH).Design and setting Clinical study in a neurosurgical intensive care unit.Patients and participants Fourteen patients with acute non-traumatic SAH were included. Fifteen healthy, age-matched volunteers served as controls for measurement of catecholamine spillover.Intervention Blood sampling for C3a, C5b-9, IL-6, IL-8 and norepinephrine kinetic determination was made within 48 h, at 72 h and on the 7th–10th day after the SAH.Measurements and results SAH patients exhibited a profound increase in the rate of norepinephrine spillover to plasma at 48 h, 72 h and 7–10 days after the insult, 3–4 times that in healthy individuals. The plasma levels of C3a, IL-6 and C5b-9 were significantly elevated at 48 h, at 72 h and 7–10 days after the SAH, but the plasma level of IL-6 decreased significantly 7–10 days after the SAH. There was no relationship between the magnitude of sympathetic activation and the levels of inflammatory markers.Conclusions Following SAH a pronounced activation of the sympathetic nervous system and the inflammatory system occurs. The lack of significant association between the rate of spillover of norepinephrine to plasma and the plasma levels of inflammatory markers indicates that the two processes, sympathetic activation and the immune response, following SAH are not quantitatively linked. In spite of a persistent high level of sympathetic activation the plasma level of IL-6 decreased significantly one week after SAH.     

Central monoamine activity in genetically distinct strains of mice following a psychogenic stressor: effects of predator exposure

The effects of psychogenic stressors, rat exposure and fox urine odor, on central monoamine functioning was assessed in two inbred strains of mice, BALB/cByJ and C57BL/6ByJ, thought to be differentially reactive to stressors. These stressors markedly increased NE utilization, as reflected by MHPG accumulation, in the locus coeruleus, hippocampus, prefrontal cortex and central amygdala. Likewise, the 5-HT metabolite, 5-HIAA, was elevated in hippocampus, prefrontal cortex and central amygdala, and to some extent DOPAC accumulation was increased in the prefrontal cortex. In most brain regions, the neurochemical effects of the stressors were comparable in the two mouse strains. However, central amygdala 5-HIAA elevations as well as DOPAC increases in the prefrontal cortex elicited by fox odor were greater in C57BL/6ByJ than in BALB/cByJ mice. Although BALB/cByJ mice are more behaviorally reactive than C57BL/6ByJ mice, and also show greater corticosterone elevations in response to neurogenic and systemic stressors, it was previously shown that differential corticosterone changes were not elicited by a predator exposure. Taken together with earlier findings, it appears that despite greater behavioral reactivity/anxiety, the strain-specific neurochemical changes elicited may be situation-specific such that the profile apparent in response to neurogenic and systemic stressors may not be evident in response to predator-related threats.     

Effects of dopamine and norepinephrine on neuronal activity of the olfactory tubercle

The effects of iontophoretic administration of norepinephrine (NE) and dopamine (DA) on olfactory tubercle (OT) neurons that respond to lateral hypothalamus (LH) or locus coeruleus (LC) electrical stimulation were studied. NE and DA decreased the frequency of OT neurons which were increased or decreased by the LH stimulation. An increased firing of OT neurons following NE or DA administration was less frequently observed. NE administration decreased the firing of OT neurons that responded to LC stimulation. These results suggest that the LC fibers which reach the OT use NE as a neurotransmitter. DA administration also suppressed the unitary discharge of OT neurons responding to LC stimulation. The increase in frequency of OT neurons observed following LH stimulation cannot be attributed to DA. The possibility that other suspected neural transmitters are involved in this effect is discussed.     

α2, α2A, α2B/2C-Adrenoceptor subtype antagonists prevent lipopolysaccharide-induced fever response in rabbits

Exogenous pyrogens, e.g., bacterial lipopolysaccharides (LPS), are thought to stimulate macrophages to release endogenous pyrogens, e.g., TNFα, IL-1 β, and IL-6, which act in the hypothalamus to produce fever. We studied the effect of different α₁⁻ and α₂-adrenoceptor subtype antagonists, applied intraperitoneally, on the febrile response induced by LPS in rabbits. Evidence was obtained that prazosin, an α₁⁻ and α_2B/2C-adrenoceptor antagonist; WB-4101, an α₁⁻ and α_2A-adrenoceptor antagonist; CH-38083, a highly selective α₂-adrenoceptor antagonist (α₂: α₁ > 2000); BRL-44408, an α_2A-adrenoceptor antagonist; and ARC-239, an α_2B/2C⁻ and also α₁-adrenoceptor antagonist, blocked the increase of colonic temperature of the rabbit produced by 2 μg/kg LPS administered intravenously without being able in themselves to affect colonic temperature. In addition, prazosin, WB-4101 and CH-38083 antagonized the fall in skin temperature that occurred at the time when the colonic temperature was rising in control animals injected with LPS. All these results suggest that norepinephrine, through stimulation of both α₁⁻andα₂⁻ (α_2A⁻andα_2B/2C⁻) adrenoceptor subtypes, is involved in producing fever in response to bacterial LPS.