Activation of hippocampal adenosine A3 receptors produces a desensitization of A1 receptor-mediated responses in rat hippocampus

The adenosine A3 receptor is expressed in brain, but the consequences of activation of this receptor on electrophysiological activity are unknown. We have characterized the actions of a selective adenosine A3 receptor agonist, 2-chloro-N6-(3-lodobenzyl)-adenosine-5'-N-methyluronamide (Cl-IB-MECA), and a selective A3 receptor antagonist, 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1, 4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS 1191), in brain slices from rat hippocampus. In the CA1 region, activation of A3 receptors had no direct effects on synaptically evoked excitatory responses, long-term potentiation, or synaptic facilitation. However, activation of A3 receptors with Cl-IB-MECA antagonized the adenosine A1 receptor-mediated inhibition of excitatory neurotransmission. The effects of Cl-IB-MECA were blocked by pretreatment with MRS 1191, which by itself had no effect on A1 receptor-mediated responses. The presynaptic inhibitory effects of baclofen and carbachol, mediated via GABA(B) and muscarinic receptors, respectively, were unaffected by Cl-IB-MECA. The maximal response to adenosine was unchanged, suggesting that the primary effect of Cl-IB-MECA was to reduce the affinity of adenosine for the receptor rather than to uncouple it. Similar effects could be demonstrated after brief superfusion with high concentrations of adenosine itself. Under normal conditions, endogenous adenosine in brain is unlikely to affect the sensitivity of A1 receptors via this mechanism. However, when brain concentrations of adenosine are elevated (e.g., during hypoxia, ischemia, or seizures), activation of A3 receptors and subsequent heterologous desensitization of A1 receptors could occur, which might limit the cerebroprotective effects of adenosine under these conditions.     

Precursors to pulmonary neoplasia

Squamous dysplasia in the bronchi has been long recognized as a precursor of lung carcinoma, particularly squamous carcinoma. Atypical adenomatous hyperplasia (AAH) has been recently implicated as a precursor to adenocarcinoma. Bronchiolar neuroendocrine cell hyperplasia has also been suggested as a precursor to some pulmonary carcinoid tumors. The atypical adenomatous hyperplasia-adenocarcinoma sequence has been likened to the adenoma-carcinoma sequence in the large intestine. AAH is commonly multifocal, and may explain multicentricity that is observed with some adenocarcinomas. AAH has been shown to have immunohistochemical, morphometric, flow cytometric and genetic abnormalities overlapping with adenocarcinoma. Bronchiolar neuroendocrine cell hyperplasia (carcinoid tumorlets) is classically associated with inflammatory lesions in the airways, but may also be multifocal and bilateral. In the latter setting, lesions may attain a size greater than 0.5 cm and be (arbitrarily) classified as carcinoid tumors.     

Morphine-induced conformational changes in human monocytes, granulocytes, and endothelial cells and in invertebrate immunocytes and microglia are mediated by nitric oxide

We evaluated the contribution of nitric oxide (NO) to morphine-induced rounding of spontaneously activated (mobile) ameboid human monocytes, granulocytes, or arterial endothelial cells and invertebrate immunocytes and microglia. Morphine induced significant rounding and inactivation of ameboid cells within 20 min except for arterial endothelial cells, which became rounded 24 h after morphine exposure. The effects of morphine on cell conformation were blocked in the presence of N-nitro-L-arginine, a nitric oxide synthase inhibitor. Treatment of cells with the NO donor, sodium nitroprusside, induced cell rounding similar to that observed following morphine exposure, suggesting that NO release may mediate morphine-induced changes in cell conformation. The contribution of NO release to morphine-induced cell rounding was determined by direct evaluation of NO concentration in real-time using a NO-specific amperometric probe. Significant increases in NO concentration were observed 2 min after morphine stimulation, whereas morphine-induced NO release was markedly impaired by pretreatment with N-nitro-L-arginine or the opiate alkaloid antagonist, naloxone. In contrast, opioid peptides failed to induce NO release, consistent with our previous observations that demonstrated the failure of opioid peptides to promote cell rounding. Taken together, these data suggest that morphine-induced NO release may be mediated by activation of the opiate alkaloid-selective, opioid peptide-insensitive micro3 receptor, and that functional coupling of morphine to NO production has been conserved during evolution and may modulate cellular activation.     

The effect of D-penicillamine on the metabolism of the basic substance of the connective tissue and the indices of the liver parenchyma in experimental cirrhosis in rats

Effect of unilateral (one leg) and bilateral (two legs) sciatectomy was studied on certain serum constituents in the male frog over a period of 3 weeks. The level of creatine kinase, acid and alkaline phosphatases, urea, glucose and proteins increased initially following sciatectomy and decreased subsequently from day 14 onwards, the per cent change being more pronounced in case of bilaterally sciatectomized frogs. The present results indicate an increase in the rate of deamination of proteins in the liver, an impairment in the transportation processes across the cell membrane and an increase in cellular lysosomal activity on sciatectomy suggesting a change either in the amount or in the rate of various enzyme reactions. It is concluded that sciatectomy induces alterations in general metabolic activities and the functional state of the animal. Altered values of various serum constituents thus permit to speculate analysis of the factor that may be contributing to the atrophic processes and the wasting of the muscle fibres known to set in the denervated muscle.     

The role of the opioid system in body adaptation and protection of the heart in stress

Literary data and the results of our own studies on the role of opioid neuropeptides in the adaptation of organism and heart protection under the action of extreme factors were analysed. The data on the cardioprotective, antiarrhythmic, neurohumoral, antistressor effects of enkephalins are grown. Possible mechanisms and the role of various populations of opiate receptors in the realisation of opioid peptides' adaptation effects are studied. The key role of endogenous opiate system in the mechanism of cardioprotective effects of natural adaptogens and adaptation is established.     

Superacid coal chemistry. 2. Model compound studies under conditions of HF:BF3:H2 catalysed mild coal liquefaction

Selected model compounds representing coal structural entities were studied under the conditions of HF-BF₃-H₂ catalysed mild coal liquefaction. Bibenzyl and diphenylmethane gave near quantitative conversion at room temperature without added hydrogen. Biphenyl, however, required hydrogen pressure at 150 °C and gave a conversion of only ≈30%. Among the model compounds containing ether linkages, dibenzyl ether and benzyl phenyl ether gave quantitative conversion at room temperature without added hydrogen. Diphenyl ether in contrast was converted (≈70% yield) only under hydrogen pressure at 155 °C. Sulphur- and nitrogen-containing model compounds were also studied. At 95 °C in the absence of hydrogen, benzyl phenyl sulphide and dibenzyl sulphide gave over 95% conversion. On the other hand diphenyl sulphide and diphenyl disulphide required hydrogen pressure at 150 °C to give conversions of ≈95%. Quinoline gave a conversion of ≈20% under hydrogen pressure at 150 °C. The formation of condensation products in these conversion processes could be suppressed by the use of a good hydrogen donor, such as isopentane.     

The dependence of shifts in arterial pressure and cardiac output during alpha-adrenoreceptor stimulation on the initial (controlled) tonus of arterial vessels in rats

A significant decrease in arterial pressure and total peripheral resistance occurred following elevation of the initial blood pressure to 160 mm Hg with mesathone in anesthetised rats. The increase in the cardiac output remaining unchanged. Vascular and cardiac mechanisms of the revealed relationships are discussed.