脊髓高位横断诱发大鼠急性胃溃疡机制的研究

在颈七水平横断大鼠脊髓以诱发急性胃溃疡。结果表明:(1)脊髓横断动物的体温随环境温度而下降,体温的下降可能是诱发溃疡的重要原因之一;(2)注射肾上腺素可减轻溃疡和防止体温下降,且两者均呈剂-效关系;(3)切除肾上腺可使脊髓横断诱发的溃疡明显减轻,如补充注射地塞米松则可使之重新加重,但体温的下降在以上情况下均不受影响;(4)脊髓横断后胃粘膜泌酸和内分泌功能的改变可能与溃疡生成有关。     

急性低氧对大鼠血液中儿茶酚胺及血小板聚集性的影响

健康ＳＤ雄性大鼠,体重２５０－３００ｇ,麻醉、气管插管,用人工呼吸机经气袋供气,自发吸入氧浓度为９％的氧氮混合气,用高效液相色谱－电化学联合检测法及电阻法检测循环血液中儿茶酚胺及全血血小权聚集性的动态变化。结果：急性低氧１５ｍｉｎ时血液中肾肾上腺素（Ａ）浓度及全血血小板聚集性显著增加（Ｐ〈０．０１）,而去甲肾上腺素（ＮＡ）浓度虽有所增加,但无统计学意义（Ｐ〉０．０５）;复氧１５ｍｉｎ时血液中儿茶酚     

Characterization of Low pH-induced Catecholamine Secretion in the Rat Adrenal Medulla

Abstract: Catecholamine (CA) secretion was evoked when the isolated rat adrenal gland was perfused with HEPES-buffered Krebs solution acidified by the addition of HCI or by gassing with 95% O₂/5% CO₂. The secretion was detectable at pH 7.0 and increased with decreasing pH until at ～6.4. The low pH-induced CA secretion consisted of two phases, an initial transient response followed by a sustained phase. An intracellular Ca²⁺ antagonist, 3,4,5-trimethoxybenzoic acid 8-(N,N-diethylamino)octyl ester, selectively inhibited the initial phase of secretion. Both of the responses were resistant to nifedipine, a blocker of voltage-gated Ca²⁺ channel, but were completely inhibited in Ca²⁺-free (1 mM EGTA containing) solution. Adrenaline was an exclusive component in CAs released by low pH. The time course and extent of intracellular acidification caused either by low pH in the external medium or by the offset of a transitory NH₄CI application had no correlation with those of the secretory responses in the corresponding period. These results suggest that extracellular acidification preferentially activates adrenaline secretive cells to evoke CA secretion and that this low pH-induced CA secretion may be mediated by dihydropyridine-insensitive Ca²⁺ influx. Furthermore, the initial transient phase of the low pH-induced CA secretion might be caused by a Ca²⁺ release from intracellular stores, which is also induced by the Ca²⁺ influx.     

Regulation of splenic contraction persists as a vestigial trait in white-blooded Antarctic fishes

In fishes, the spleen can function as an important reservoir for red blood cells (RBCs), which, following splenic contraction, may be released into the circulation to increase haematocrit during energy-demanding activities. This trait is particularly pronounced in red-blooded Antarctic fishes in which the spleen can sequester a large proportion of RBCs during rest, thereby reducing blood viscosity, which may serve as an adaptation to life in cold environments. In one species, Pagothenia borchgrevinki, it has previously been shown that splenic contraction primarily depends on cholinergic stimulation. The aim of the present study was to investigate the regulation of splenic contraction in five other Antarctic fish species, three red-blooded notothenioids (Dissostichus mawsoni Norman, 1937, Gobionotothen gibberifrons Lönnberg, 1905, Notothenia coriiceps Richardson 1844) and two white-blooded “icefish” (Chaenocephalus aceratus Lönnberg, 1906 and Champsocephalus gunnari Lönnberg, 1905), which lack haemoglobin and RBCs, but nevertheless possess a large spleen. In all species, splenic strips constricted in response to both cholinergic (carbachol) and adrenergic (adrenaline) agonists. Surprisingly, in the two species of icefish, the spleen responded with similar sensitivity to red-blooded species, despite contraction being of little obvious benefit for releasing RBCs into the circulation. Although the icefish lineage lost functional haemoglobin before diversifying over the past 7.8–4.8 millions of years, they retain the capacity to contract the spleen, likely as a vestige inherited from their red-blooded ancestors.     

Adrenaline stimulates H2O2 generation in liver via NADPH oxidase

It is known that adrenaline promotes hydroxyl radical generation in isolated rat hepatocytes. The aim of this work was to investigate a potential role of NADPH oxidase (Nox) isoforms for an oxidative stress signal in response to adrenaline in hepatocytes. Enriched plasma membranes from isolated rat liver cells were prepared for this purpose. These membranes showed catalytic activity of Nox isoforms, probably Nox 2 based on its complete inhibition with specific antibodies. NADPH was oxidized to convert O₂ into superoxide radical, later transformed into H₂O₂. This enzymatic activity requires previous activation with either 3 mM Mn²⁺ or guanosine 5′-0-(3-thiotriphosphate) (GTPγS) plus adrenaline. Experimental conditions for activation and catalytic steps were set up: ATP was not required; S_0.5 for NADPH was 44 μM; S_0.5 for FAD was 8 μM; NADH up to 1 mM was not substrate, and diphenyleneiodonium was inhibitory. Activation with GTPγS plus adrenaline was dose- and Ca²⁺-dependent and proceeded through α₁-adrenergic receptors (AR), whereas β-AR stimulation resulted in inhibition of Nox activity. These results lead us to propose H₂O₂ as additional transduction signal for adrenaline response in hepatic cells.     

High Performance Liquid Chromatography of Hydroperoxides Formed by Autoxidation of Vegetable Oils

Trilinoleoylglycerol (TL) was autoxidized at 37°C in the dark. Monohydroperoxides (MHP) obtained from the oxidized products were analyzed by high performance liquid chromatography (HPLC). Several peaks which appeared in the chromatogram were identified by infrared (IR), gas chromatography mass spectrometry (GC-MS) and enzymatic hydrolysis. Some positional and geometrical isomers of their hydroperoxy fatty acid components were separated using both absorption and reversed phase systems. Furthermore, 1-hydroperoxylinoleoyl-2,3-dilinoleoyl-glycerol and 1,3-dilinoleoyl-2-hydroperoxylinoleoylglycerol were partly separated by HPLC using an absorption system. MHP obtained from autoxidized corn oil, safflower oil and soybean oil were separated into some peaks by HPLC, although resolution into the individual isomers was incomplete. When oxidized oils were subjected to HPLC analysis directly, a linear relationship was observed between the peak areas of MHP and peroxide value in the range of 10 ~ 50 meq/kg.     

Activation and inhibition of succinate-dependent Ca2+ transport in liver mitochondria during adaptation

Succinate-dependent Ca²⁺ accumulation was investigated in rat liver mitochondria and in operation biopsies of patients under states either with prevalence of adrenergic influences (administration of activating doses of adrenaline, acute phase of immobilization stress, initial period after allogenic transplantation, and acute phase of myocardial infarction) or with prevalence of the reciprocal mediator acetylcholine (late period after transplantation, chronic ulcer disease of stomach and duodenum). Adrenaline prevalence leads to increase of succinate-dependent ATP synthesis and Ca²⁺ accumulation, which is due to known activation of succinate oxidation. However, together with activation, inhibition of these processes was revealed. The inhibition phase prevails under chronic pathology. Therefore, reciprocal regulation of succinate oxidation and succinate-dependent Ca²⁺ transport in mitochondria occurs in the body in the course of adaptation. The reciprocal regulation of mitochondrial processes is considered as a mechanism of reciprocal regulation of physiological functions.     

α2—肾上腺素体介导大鼠主动脉收缩的特性

为阐明功能性α2－肾上腺素受体（α2－AR）的特性及其与α1－AR的相互关系,以离体大鼠主动脉为模型,进行收缩功能实验,发现在大鼠主动脉中,α1－AR和α2－AR产可介导其收缩效应并以α1－AR折作用为主,α1－AR可增强α2－AR介导的收缩效应,而α2－AR则对α1－AR介导的收缩效应无影响,在不可逆阻断α1－AR而保留α2－AR的条件下,α2－AR介导的缩血管效应消失,仅在阈值浓度的KCl存在下才能显示,且收缩幅度较对照组显著降低,结果表明,在离体大鼠主体动脉中存在功能性α2－AR,α2－AR的缩血管作用依赖于α1－AR的激动,其最大收缩反应远远小于α1－AR。     

Differential contribution of syntaxin 1 and SNAP-25 to secretion in noradrenergic and adrenergic chromaffin cells

We used botulinum neurotoxins (BoNT) to examine whether differences in the secretory activity of noradrenergic and adrenergic chromaffin cells are related to differences in the exocytotic machinery of these two types of bovine adrenal medulla cells. Cleavage of syntaxin and SNAP-25 by BoNT/C1 decreased in a dose-dependent way the release of both noradrenaline and adrenaline, but noradrenaline release was more sensitive to BoNT/C1. Cleavage of SNAP-25 by BoNT/A also had a larger inhibitory effect on noradrenaline release than on adrenaline release. Neither BoNT/C1 nor BoNT/A affected the intracellular Ca2+ responses induced by K+-depolarisation, and the extent of the inhibition of K+-evoked catecholamine release by selective blockers of voltage-gated Ca2+ channels was not affected by BoNT/C1. Therefore, our data do not support the hypothesis of a regulatory effect of syntaxin or SNAP-25 on the activity of Ca2+ channels. The lower sensitivity of adrenaline release to BoNT was not due to a reduced ability of the toxins to enter or to cleave their protein targets in adrenergic cells, since immunoblot analysis showed the cleavage of a larger fraction of syntaxin 1A in adrenergic cells, as compared to the cleavage in noradrenergic cells. The immunoblot analysis also showed larger amounts of syntaxin 1A in noradrenergic chromaffin cells than in adrenergic cells. Thus, in spite of a greater cleavage of syntaxin 1A in adrenergic cells by BoNT/C1, adrenaline release was less sensitive to BoNT/C1, suggesting that the release process in noradrenergic cells might be more dependent on syntaxin 1A and SNAP-25, as compared to adrenergic cells.     

Beef cattle selected for increased muscularity have a reduced muscle response and increased adipose tissue response to adrenaline

The aim of this experiment was to evaluate the impact of selection for greater muscling on the adrenaline responsiveness of muscle, adipose and liver tissue, as reflected by changes in plasma levels of the intermediary metabolites lactate, non-esterified fatty acids (NEFA) and glucose. This study used 18-month-old steers from an Angus herd visually assessed and selected for divergence in muscling for over 15 years. Ten low muscled (Low), 11 high muscled (High) and 3 high muscled heterozygotes for myostatin mutation (High(Het)) steers were challenged with adrenaline doses ranging between 0.2 to 3.0 μg/kg live weight. For each challenge, 16 blood samples were taken between -30 and 130 min relative to adrenaline administration. Plasma was analysed for NEFA, lactate and glucose concentration and area under curve (AUC) over time was calculated to reflect the tissue responses to adrenaline. Sixteen basal plasma samples from each animal were also assayed for growth hormone. Muscle glycogen and lactate concentration were analysed from four muscle biopsies taken from the semimembranosus, semitendinosus and longissimus thoracis et lumborum of each animal at 14, 90 and 150 days on an ad libitum grain-based diet and at slaughter on day 157. In response to the adrenaline challenges, the High steers had 30% lower lactate AUC than the Low steers at challenges greater than 2 μg/kg live weight, indicating lower muscle responsiveness at the highest adrenaline doses. Aligning with this decrease in muscle response in the High animals were the muscle glycogen concentrations which were 6.1% higher in the High steers. These results suggest that selection for muscling could reduce the incidence of dark, firm, dry meat that is caused by low levels of glycogen at slaughter. At all levels of adrenaline challenge, the High steers had at least 30% greater NEFA AUC, indicating that their adipose tissue was more responsive to adrenaline, resulting in greater lipolysis. In agreement with this response, the High steers had a higher plasma growth hormone concentration, which is likely to have contributed to the increased lipolysis evident in these animals in response to adrenaline. This difference in lipolysis may in part explain the reduced fatness of muscular cattle. There was no effect of selection for muscling on liver responsiveness to adrenaline.