scholarly journals Neuroanesthesia and Intensive Care Isoflurane tolerance against focal cerebral ischemia is attenuated by adenosine A1 receptor antagonists

2006 ◽  
Vol 53 (2) ◽  
pp. 194-201 ◽  
Author(s):  
Yanhong Liu ◽  
Lize Xiong ◽  
Shaoyang Chen ◽  
Qiang Wang
Keyword(s):  
Intensive Care ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Adenosine A1 Receptor ◽  
Receptor Antagonists ◽  
Adenosine A1 ◽  
A1 Receptor

Upregulated renal adenosine A1 receptors augment PKC and glucose transport but inhibit proliferation

1996 ◽  
Vol 270 (2) ◽  
pp. F263-F274 ◽  
Author(s):  
R. Coulson ◽  
P. S. Proch ◽  
R. A. Olsson ◽  
C. E. Chalfant ◽  
D. R. Cooper
Keyword(s):  
Cell Proliferation ◽  
Protein Kinase ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Adenosine Receptor ◽  
Adenosine A1 Receptor ◽  
Receptor Antagonists ◽  
Caffeine Treatment ◽  
Adenosine A1 ◽  
A1 Receptor

Adenosine A1 receptor densities were increased in cultured LLC-PK1 and OK cells by chronic treatment with the adenosine receptor antagonists 1,3,7-trimethylxanthine (caffeine, 1 mM) and 1,3-dimethyl-8-cyclopentylxanthine [cyclopentyltheophylline (CPT), < or = 0.4 mM], respectively. The A1 receptor number per cell was increased twofold by 10-day treatments with 1 mM caffeine or 0.1 mM CPT, and the sodium-coupled glucose uptake was augmented twofold by 1 mM caffeine and sevenfold by 0.1 microM CPT (higher doses of CPT were progressively less stimulatory). Glucose uptake was blocked by acute (2-h) treatment with CPT, adenosine deaminase, or calphostin C. Caffeine (1 mM) or CPT (> or = 0.1 mM) inhibited cell proliferation for the first 10 days, then cell growth assumed a normal proliferative rate despite continued presence of antagonist. Cytosolic protein kinase C (PKC) beta-isoform immunoactivity and PKC-beta II mRNA were elevated at least twofold during 10 days of 0.1 mM CPT or 1 mM caffeine treatment. The sustained elevation in sodium-glucose symport and PKC activity observed with adenosine receptor antagonists was similar to acute (2-h) effects of the adenosine A1 agonist R(-)-N6-phenylisopropyladenosine (R-PIA, 0.1-1 microM). Moreover, cell proliferation was increased by adenosine (0.1 microM R-PIA), whereas Na-K-adenosinetriphosphatase activity was unaltered with chronic antagonist or acute adenosine treatments. Caffeine treatment may have some non-adenosine A1 receptor-mediated actions, because it slightly (30%) augmented protein kinase A activity. It is concluded that chronic exposure of proximal tubule cells to caffeine or CPT augments PKC and sodium-glucose transport but retards cell proliferation mainly via adenosine A1 receptor-mediated mechanisms.

Adenosine pre- and postsynaptic modulation of glutamate-dependent calcium activity in hypothalamic neurons

1995 ◽  
Vol 74 (5) ◽  
pp. 2150-2162 ◽  
Author(s):  
K. Obrietan ◽  
A. B. Belousov ◽  
H. C. Heller ◽  
A. N. van den Pol
Keyword(s):  
Electrical Activity ◽  
Glutamate Receptor ◽  
Receptor Agonist ◽  
Adenosine A1 Receptor ◽  
Receptor Antagonists ◽  
Hypothalamic Neurons ◽  
Postsynaptic Potentials ◽  
Adenosine A1 ◽  
Hypothalamic Cells ◽  
A1 Receptor

1. Within the hypothalamus, adenosine has been reported to influence temperature regulation, sleep homeostasis, and endocrine secretions. The effects of adenosine on hypothalamic neurons have not been studied at the cellular level. Adenosine (5 nM-30 microM) showed no influence on intracellular Ca2+ or electrical activity in the presence of glutamate receptor antagonists D-2-amino-5-phosphonovalerate and 6-cyano-7-nitroquinoxaline-2,3-dione; consequently, we examined the role of adenosine in modulating the activity of glutamate in cultured hypothalamic neurons (n > 1,700) with fura-2 Ca2+ digital imaging and whole cell patch-clamp electrophysiology in the absence of glutamate receptor block. 2. When glutamate receptors were not blocked, adenosine (1-30 microM) and the selective adenosine A1 receptor agonist N6-cyclopentyl adenosine (CPA; 5 nM-1 microM) caused a large reduction in intracellular Ca2+ and electrical activity, suggesting that glutamate neurotransmission was critical for an effect of adenosine to be detected. Neuronal Ca2+ levels were reversibly depressed by CPA (50 nM), with a maximum depression of 90%, and these effects were blocked by coadministration of the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). 3. Ca2+ levels in immature neurons before the time of synaptogenesis were not affected by adenosine. Adenosine A1 receptor activation suppressed glutamate-mediated Ca2+ activity in neurons in vitro 8 to 73 days. 4. Adenosine (1 or 10 microM) caused a hyperpolarization of membrane potential and a reduction of large postsynaptic potentials arising from endogenously released glutamate. The administration of low concentrations of CPA (5 nM) decreased the frequency of glutamate-mediated, neuronally synchronized Ca2+ transients and the frequency of postsynaptic potentials. 5. To compare the relative effects of adenosine on hypothalamic neurons with cells from other brain regions, we assayed the effects of CPA on glutamate-mediated Ca2+ in hippocampal and cortical cultures. CPA (50 nM) reversibly depressed glutamate-mediated Ca2+ rises in hypothalamic neurons by 35%, compared with 54% in hippocampal neurons and 46% in cortical neurons. 6. If it does play a functional role, adenosine should be released by hypothalamic cells. In some neurons the adenosine A1 receptor antagonists cyclopentyltheophylline or DPCPX caused an increase in intracellular Ca2+, suggesting that adenosine was secreted by hypothalamic cells, tonically depressing glutamate-enhanced neuronal Ca2+. 7. To determine whether adenosine could exert a postsynaptic effect, we coapplied it with glutamate agonists in the presence of tetrodotoxin. Within subpopulations of hypothalamic neurons, adenosine and CPA either inhibited (18% of total neurons) or potentiated (6% of total neurons) responses to glutamate, N-methyl-D-aspartate, and kainate by > or = 20%. 8. In contrast to the modest effects found in neurons, responses of hypothalamic astrocytes to the application of glutamate or the metabotropic glutamate receptor agonist (+/-)-trans-1-amino-1,3-cyclopentanedicarboxylic acid were strongly potentiated by adenosine (mean +225%) and CPA. 9. Together, these findings suggest that adenosine exerts a major presynaptic effect and a minor postsynaptic effect in the modulation of glutamate neurotransmission in the hypothalamus, where it can play a significant role in blocking a large part of the glutamate-induced Ca2+ rise. In the absence of glutamate transmission, adenosine has relatively little effect on either neuronal intracellular Ca2+ or electrical activity.

scholarly journals 2–Benzylidene–1–Indanone Analogues as Dual Adenosine A1/A2a Receptor Antagonists for the Potential Treatment of Neurological Conditions

Drug Research ◽  
2019 ◽  
Vol 69 (07) ◽  
pp. 382-391 ◽  
Author(s):  
HelenaDorathea Janse van Rensburg ◽  
LesetjaJ. Legoabe ◽  
Gisella Terre’Blanche ◽  
MiethaM. Van der Walt
Keyword(s):  
Radioligand Binding ◽  
Aldol Condensation ◽  
Adenosine A1 Receptor ◽  
Potential Treatment ◽  
Receptor Antagonists ◽  
A2a Receptor ◽  
Adenosine A1 ◽  
A1 Receptor ◽  
Neurological Conditions ◽  
Aldol Condensation Reactions

AbstractPrevious studies explored 2-benzylidine-1-tetralone derivatives as innovative adenosine A1 and A2A receptor antagonists for alternative non-dopaminergic treatment of Parkinson’s disease. This study’s aim is to investigate structurally related 2-benzylidene-1-indanones with substitutions on ring A and B as novel, potent and selective adenosine A1 and A2A receptor blockers. 2-Benzylidene-1-indanone derivatives were synthesised via acid catalysed aldol condensation reactions and evaluated via radioligand binding assays to ascertain structure activity relationships to govern A1 and A2A AR affinity. The results indicated that hydroxy substitution at C4 of ring A and meta (3’), or para (4’) substitution on ring B of the 2-benzylidene-1-indanone scaffold (2c) is preferred over substitution at C5 (2d) or C6 (2e) of ring A for adenosine A1 receptor activity and selectivity in the micromolar range. Furthermore, substitution at the meta (3’) position of ring B with chlorine lead to the highly potent and selective adenosine A2A receptor antagonist, compound 2 h. Compound 2c and the 2q behaved as adenosine A1 receptor antagonists in the performed GTP shift assays. In view of these findings, compounds 2c, 2 h, 2q and 2p are potent and selective adenosine A1 and A2A receptor antagonists for the potential treatment of neurological conditions.

5'-Deoxy congeners of 9-(3-amido-3-deoxy-β-D-xylofuranosyl)-N6-cyclopentyladenine: New adenosine A1 receptor antagonists

1999 ◽  
Author(s):  
Serge Van Calenbergh ◽  
Andreas Link ◽  
Shelly Fujikawa ◽  
Veerle Vanheusden ◽  
Denis De Keukeleire ◽  
...  
Keyword(s):  
Adenosine A1 Receptor ◽  
Receptor Antagonists ◽  
Adenosine A1 ◽  
A1 Receptor
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