Pre‐conditioning activates adenosine utilization in a cost‐effective way during myocardial ischaemia

During pre‐conditioning the interstitial concentration of adenosine, in contrast to lactate, presents a die‐away curve‐pattern for every successive episode of ischaemia. This die‐away pattern might not necessarily be attributed to diminished adenosine production. The present study was undertaken to investigate whether pre‐conditioning alters the metabolic turnover of adenosine as observed by the lactate production during ischaemia. Interstitial levels of metabolites in pre‐conditioned (n=21) and non‐preconditioned (n=21) porcine hearts were monitored with microdialysis probes inserted in both ischaemic and non‐ischaemic tissue in an open chest heart model. Three subgroups perturbated with either plain microdialysis buffer (control), buffer containing adenosine (375 μM ), or buffer containing deoxyadenosine (375 μM ) were studied. All animals were subjected to 90 min of equilibrium microdialysis before 40 min of regional myocardial ischaemia and 120 min of reperfusion. Pre‐conditioning consisted of four repetitive episodes of 10 min of ischaemia and 20 min of reperfusion. Significantly higher levels of inosine and lactate were found in the ischaemic tissue of the pre‐conditioned subgroup receiving adenosine (P < 0.05) compared with the other two subgroups receiving deoxyadenosine and plain buffer, respectively. This difference was only valid for pre‐conditioned ischaemic myocardium, and hence equal amounts of inosine and lactate were produced in the non‐preconditioned ischaemic myocardium regardless of the presence of adenosine or deoxyadenosine. In the non‐ischaemic myocardium baseline levels of metabolites were measured in all subgroups. Pre‐conditioning favoured degradation of exogenous adenosine to inosine successively ending up in enhanced lactate production. This was probably because of the involvement of the hexose monophosphate pathway in the pre‐conditioned ischaemic myocardium. This route may therefore be supplementary in energy metabolism as a metabolic flow can be started by adenosine ending up in lactate without initial adenosine 5′‐triphosphate (ATP) investment. Utilization of adenosine in this way may also explain the successive die‐away pattern of adenosine seen in consecutive pre‐conditioning cycles.     

腺苷A2a受体在炎症反应中的作用

腺苷广泛分布于全身各组织器官,可通过与细胞表面相应G-蛋白偶联受体结合发挥抑制炎症反应,对抗缺血/缺氧和免疫调节等生物学作用.目前发现腺苷受体有4种亚型,即A1R、A2aR、A2bR和A3R.其中A2a腺苷受体(A2aR)广泛分布于神经胶质细胞,巨噬细胞,树突状细胞,肥大细胞,自然杀伤细胞等免疫细胞及内皮细胞和上皮细胞中,在相应的腺苷配体作用下,可通过腺苷-腺苷受体系统介导炎症反应和发挥免疫调节作用.     

Inhibitory effect of adenosine on electrically evoked contractions in the rat vas deferens: pharmacological characterization

The inhibitory effects of adenosine as well as its related analogues on the contractile response of the rat vas deferens to field stimulation were compared in the absence and in the presence of nitrobenzylthioguanosine (NBTGR), a potent adenosine uptake inhibitor. In the presence of NBTGR, the order of potency was N6-cyclohexyladenosine (CHA) greater than or equal to L-N6-phenylisopropyladenosine (L-PIA) greater than 2-chloroadenosine greater than D-N6-phenylisopropyladenosine (D-PIA) greater than or equal to adenosine greater than 2'-deoxyadenosine. The inhibitory effect of adenosine but not that of clonidine, beta-endorphin and somatostatin was blocked by 1,3-diethyl-8-phenylxanthine (DPX, pA2 = 7.2), a potent P1-purinergic antagonist. The results suggest that adenosine inhibited the electrically evoked contractions of the rat vas deferens via the activation of the A1 subtype of P1-purinergic receptors.     

Membrane-bound choline acetyltransferase in Torpedo electric organ: A marker for synaptosomal plasma membranes?

The enzyme choline-O-acetyltransferase catalyses the biosynthesis of acetylcholine from acetyl coenzyme A and choline and is considered as one of the best markers for cholinergic nerve endings. The distribution of this enzymatic activity was analysed during the purification of plasma membranes of purely cholinergic nerve endings isolated from the electric organ of the fish Torpedo marmorata. This tissue, which receives a profuse and purely cholinergic innervation, can be considered as being a "giant" neuromuscular synapse. The isolated nerve endings (synaptosomes) were first osmotically disrupted and their plasma membranes isolated by equilibrium density centrifugation (discontinuous followed by continuous sucrose gradients). Choline acetyltransferase activity was found to exist in three forms: (1) a soluble form (the major one) present in the cytoplasm of the nerve endings, (2) a form which is ionically associated with membranes and which can be solubilized by washing exhaustively the membrane fraction with solutions of high ionic strength (0.5 M NaCl) and (iii) a form which is non-ionically bound to membranes and cannot be solubilized with high salt solution. The soluble and the non-ionically bound activities exhibited very similar affinities for choline (1.34 and 1.64 mM, respectively). The non-ionically membrane-associated form of choline acetyltransferase was found to "copurify" with the cholinergic synaptosomal plasma membranes of Torpedo, its specific activity being increased from 122 (crude fraction) to 475 (purified membrane fraction) nmol/h/mg protein. An enrichment was also observed for another cholinergic marker, the enzyme acetylcholinesterase, but not for the nicotinic receptor to acetylcholine, a marker for postsynaptic membranes. No choline acetyltransferase activity could be detected in preparations of synaptic vesicles that were highly purified from the electric organ. Also, the non-ionically associated form of choline acetyltransferase activity was hardly detectable (2.4 nmol/h/mg protein) in fractions enriched in axonal membranes prepared from the cholinergic electric nerves innervating the electric organ. The partition into soluble and membrane-bound activity was also analysed for choline acetyltransferase present in human placenta, a rich source for the enzyme but a non-innervated tissue. In this case the great majority of the enzyme appeared as soluble activity. Very low levels of non-ionically membrane-bound activity were found to be present in a crude membrane fraction from human placenta (2.8 nmol/h/mg protein).(ABSTRACT TRUNCATED AT 400 WORDS)     

Comparison of β-adrenoceptors mediating vasodilatation in canine subcutaneous adipose tissue and skeletal muscle

Blood flow changes in response to various drugs in simultaneously autoperfused canine subcutaneous adipose tissue and gracilis muscle were compared to study the vascular β-adrenoceptors. Compared to isoprenaline the β₂-selective agonist salbutamol was 4–6 times more potent as a vasodilator in the muscle than in adipose tissue. Furthermore two β₁-selective agonists (Tazolol and H80/62) caused vasodilatation in adipose tissue but not in the gracilis muscle. When given by close i.a. injection after β-adrenoceptor blockade, adrenaline was a more potent vasoconstrictor than noradrenaline in both tissues. Before β-blockade, however, noradrenaline was the more potent vasoconstrictor in the gracilis muscle whereas adrenaline was more potent in adipose tissue. Intravenous infusion of adrenaline in doses causing vasodilatation in the muscle caused vasoconstriction in adipose tissue whereas intravenous infusion of noradrenaline caused vasoconstriction in both tissues. The present findings suggest that the β-adrenoceptors mediating vasodilatation in skeletal muscle are mainly of the β₂-type, whereas β₁-adrenoceptors seem to predominate in subcutaneous adipose tissue. Since adrenaline is a much more potent β₂- than β₁-agonist, these differences point to different roles of intravascular adrenaline in the two sites. In skeletal muscle circulating adrenaline is mainly a vasodilator whereas in subcutaneous adipose tissue it mainly acts as a vasoconstrictor.     

ADA、ACE、LDH、CEA的联合检测在结核性和恶性胸腔积液中的鉴别诊断价值

目的测定血清和胸水中腺苷脱氨酶（ADA）、血管紧张素转化酶（ACE）、乳酸脱氢酶（LDH）与癌胚抗原（CEA）的水平,探讨其指标联合检测对结核性和恶性胸水的鉴别诊断意义。方法对临床已确诊的72例胸腔积液患者（结核性40例,恶性32例）的胸水和血清分别采用酶免疫法和化学发光法进行ADA、ACE、LDH和CEA含量测定。结果结核性胸水中ADA的含量为（60.2±20.10）U/L,ACE的含量为（35±9.6）U/L,LDH的含量为（338±41）U/L,CEA的含量为（12.8±5.82）μg/L;在恶性胸水中,ADA为（11.02±5.23）U/L,ACE为（16±11.0）U/L,LDH为（379±69.0）U/L,CEA为（39.9±19.7）μg/L。结核性胸水ADA和ACE含量较恶性胸水组明显增高（P〈0.01）,CEA在恶性胸水中含量较结核性胸水组明显增高（P〈0.01）。胸水中ADA和ACE的检测对结性性胸膜积液诊断的敏感性分别为84.3%、87.5%,特异性分别为87.5%、80.0%;而胸水中LDH和CEA的检测对恶性胸膜积液诊断的敏感分别为84.3%、75.0%,特异性分别为80.0%、93.0%。四项指标联合检测敏感性性为78.1%,特异性为97.5%,较单一指标的特异性高。结论胸水中ADA、ACE、LDH和CEA的联合检测对结核性和恶性胸水的鉴别诊断具有一定价值,有助于临床胸水性质的诊断。     

Three Kinds of Foamy Cells in the Spleen: Comparative Histochemical and Ultrastructural Studies

By light and electron microscopy, we observed foamy cells in the spleens from a patient with hemolytic anemia due to red cell adenosine deaminase (ADA) overproduction, a patient with rheumatoid arthritis (RA) treated with gold, and patients with idiopathic thrombocytopenic purpura (ITP)

The foamy cells associated with red cell ADA overproduction were essentially similar to Gaucher-like cells described in patients with thalassemia, and it was suggested that the accelerated destruction of red cells was one of the factors responsible for the development of foamy cells. Foamy cells in ITP and RA were closely associated with an increased destruction of platelets in the spleen. Morphologic transitions between phagocytosed platelets and myelinlike materials were traced in these disorders. In RA, however, foamy cells were heterogeneous from an ultrastructural standpoint, with different cytoplasmic inclusions. In addition to myelinlike materials, dense bodies, vacuoles with flocculent materials, and gold were noted in most of foamy cells. As gold compounds are known to inhibit lysosomal enzymes, we surmise that an acquired disturbance in lysosomal digestion is partially responsible for the accumulation of intermediate metabolites.

In the pathogenesis of foamy cells associated with blood cell dyscrasia, the accelerated destruction of blood cells and/or acquired disorders in catabolic pathways within the macrophages are suggested to be the underlying mechanism of an intralysosomal accumulation of incompletely degraded cellular debris.     

Adenosine receptor density and the depression of evoked neuronal activity in the rat hippocampus in vitro

The relationship between the heterogeneous distribution of A-1 adenosine receptors and the capacity of adenosine to depress neuronal activity was examined in the rat hippocampus. Utilizing autoradiographic techniques, the distribution of A-1 adenosine receptors was assessed by the binding of [3H]cyclohexyladenosine ([3H]CHA) to cryostat sections of rat brain. The apical dendritic region of CA1 showed a differential distribution of adenosine receptors between the stratum radiatum and stratum lacunosum/moleculare. The physiological relevance of this binding difference was studied in the hippocampal slice by examining the capacity of adenosine to depress evoked potentials in these two strata. It was observed that the receptor differences correlated with differential sensitivities to adenosine modulation of the evoked potentials. These data suggest that receptor density, as shown by binding techniques, may provide not only a qualitative but also a quantitative map of the sites of adenosine action.     

Effect of adenosine and β-endorphin on contractions of the vas deferens of rats differing in predisposition to ethanol

Laboratory for the Search for and Study of Agents for Prevention and Treatment of Drug Addictions, Research Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. V. Val'dman.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 108, No. 12, pp. 700–702, December, 1989.     

Cytochemical localization of 5'-nucleotidase activity in retinal photoreceptor cells

Further cytochemical studies on the ultrastructural localization of 5'-nucleotidase in the rat retina have revealed activity to be associated with the complex synapses formed by the rod spherules of the receptors and the bipolar and horizontal cell processes. Activity was also seen on the axolemma of receptor fibers. In the rod inner segment strong reaction product is located intracellularly. In the rod outer segment the enzyme appears to be located only on the cytoplasmic side of the disc membrane and not intradiscally . Retinal pigment cells are rich in 5'-nucleotidase. Their microvilli accompany the tips of the receptor cells and show enzyme activity in an ecto position. A role for 5'-nucleotidase is possible in the metabolism of guanylate and adenylate nucleotides both of which are important for visual transduction processes.