scholarly journals Adenosine, a “Retaliatory” Metabolite, Promotes Anoxia Tolerance in Turtle Brain

1993 ◽  
Vol 13 (4) ◽  
pp. 728-732 ◽  
Author(s):  
Miguel A. Pérez-Pinzón ◽  
Peter L. Lutz ◽  
Thomas J. Sick ◽  
Myron Rosenthal
Keyword(s):  
Adenosine Receptor ◽  
Extracellular Space ◽  
Ion Homeostasis ◽  
Extracellular Potassium ◽  
Anoxia Tolerance ◽  
Adenosine Release ◽  
Turtle Species ◽  
Adenosine Receptor Antagonist ◽  
Anoxic Depolarization ◽  
Ion Activity

Contrary to what is found in most vertebrates, the brains of certain turtle species maintain ATP levels and ion homeostasis and survive prolonged anoxia. The hypothesis tested here is that the release of adenosine and its binding to A1 receptors are essential for this anoxic tolerance. Studies were conducted in the isolated turtle cerebellum, which did release adenosine to the extracellular space during anoxia. When adenosine receptor antagonists [theophylline, 8-cyclopentyltheophylline (CPT), or 8-cyclopentyl-1,3-dipropylxanthine (DPCPX)] were added to the superfusate under control conditions, they had no effect on extracellular potassium ion activity ([K+]o). During anoxia, however, these antagonists provoked maximal efflux of K+ (anoxic depolarization). Anoxic depolarization occurred earlier during anoxia with theophylline (a nonspecific adenosine receptor antagonist) than with CPT or DPCPX, which specifically block A1 receptors. Therefore, adenosine release and effects mediated by A1 receptors are essential to anoxia tolerance in turtle brain.

Slow ATP loss and the defense of ion homeostasis in the anoxic frog brain

2001 ◽  
Vol 204 (20) ◽  
pp. 3547-3551
Author(s):  
Debra L. Knickerbocker ◽  
Peter L. Lutz
Keyword(s):  
Initial Phase ◽  
Ion Homeostasis ◽  
Atp Depletion ◽  
Neuronal Membrane ◽  
Anoxia Tolerance ◽  
Frog Brain ◽  
Atp Levels ◽  
Anoxic Depolarization ◽  
Rate Of Increase ◽  
The Brain

SUMMARY For most vertebrates, cutting off the oxygen supply to the brain results in a rapid (within minutes) loss of ATP, the failure of ATP-dependent ion-transport process, subsequent anoxic depolarization of neuronal membrane potential and consequential neuronal death. The few species that survive brain anoxia for days or months, such as the freshwater turtle Trachemys scripta, avoid anoxic depolarization and maintain brain ATP levels through a coordinated downregulation of brain energy demand processes. The frog Rana pipiens represents an intermediate in anoxia-tolerance, being able to survive brain anoxia for hours. However, the anoxic frog brain does not defend its energy stores. Instead, anoxia-tolerance appears to be related to a retarded rate of ATP depletion. To investigate the relationship between this slow ATP depletion and the loss of ionic homeostasis, cerebral extracellular K+ concentrations were monitored and ATP levels measured during anoxia, during the initial phase of anoxic depolarization and during complete anoxic depolarization. Extracellular K+ levels were maintained at normoxic levels for at least 3 h of anoxia, while ATP content decreased by 35 %. When ATP levels reached 0.33±0.06 mmol l–1 (mean ± s.e.m., N=5), extracellular K+ levels slowly started to increase. This value is thought to represent a critical ATP concentration for the maintenance of ion homeostasis. When extracellular [K+] reached an inflection value of 4.77±0.84 mmol l–1 (mean ± s.e.m., N=5), approximately 1 h later, the brain quickly depolarized. Part of the reduction in ATP demand was attributable to an approximately 50 % decrease in the rate of K+ efflux from the anoxic frog brain, which would also contribute to the retarded rate of increase in extracellular [K+] during the initial phase of anoxic depolarization. However, unlike the anoxia-tolerant turtle brain, adenosine did not appear to be involved in the downregulation of K+ leakage in the frog brain. The increased anoxia-tolerance of the frog brain is thought to be a matter more of slow death than of enhanced protective mechanisms.

scholarly journals Ion Channel Involvement in Anoxic Depolarization Induced by Cardiac Arrest in Rat Brain

1995 ◽  
Vol 15 (4) ◽  
pp. 587-594 ◽  
Author(s):  
Yaxia Xie ◽  
Elke Zacharias ◽  
Patricia Hoff ◽  
Frank Tegtmeier
Keyword(s):  
Cardiac Arrest ◽  
Ion Channel ◽  
Rat Brain ◽  
Ion Homeostasis ◽  
Rapid Decline ◽  
Channel Blockers ◽  
Mk 801 ◽  
Anoxic Depolarization ◽  
Ion Activity ◽  
Cellular Ca

Anoxic depolarization (AD) and failure of ion homeostasis play an important role in ischemia-induced neuronal injury. In the present study, different drugs with known ion-channel-modulating properties were examined for their ability to interfere with cardiac-arrest-elicited AD and with the changes in the extracellular ion activity in rat brain. Our results indicate that only drugs primarily blocking membrane Na+ permeability (NBQX, R56865, and flunarizine) delayed the occurrence of AD, while compounds affecting cellular Ca2+ load (MK-801 and nimodipine) did not influence the latency time. The ischemia-induced [Na+]e reduction was attenuated by R56865. Blockade of the ATP-sensitive K+ channels with glibenclamide reduced the [K+]e increase upon ischemia, indicating an involvement of the KATP channels in ischemia-induced K+ efflux. The KATP channel opener cromakalim did not affect the AD or the [K+]e concentration. The ischemia-induced rapid decline of extracellular calcium was attenuated by receptor-operated Ca2+ channel blockers MK-801 and NBQX, but not by the voltage-operated Ca2+ channel blocker nimodipine, R56865, and flunarizine.

scholarly journals EEG Suppression and Anoxic Depolarization: Influences on Cerebral Oxygenation during Ischemia

1991 ◽  
Vol 11 (3) ◽  
pp. 407-415 ◽  
Author(s):  
Cesar N. Raffin ◽  
Madaline Harrison ◽  
Thomas J. Sick ◽  
Myron Rosenthal
Keyword(s):  
Cerebral Ischemia ◽  
Cerebral Oxygenation ◽  
Extracellular Potassium ◽  
Tissue Oxygen ◽  
Vessel Occlusion ◽  
Anoxic Depolarization ◽  
Occlusion Model ◽  
Oxygen Stores ◽  
Ion Activity ◽  
Energy Failure

Cerebral ischemia provokes sequential changes that include EEG suppression, anoxic depolarization (AD) with maximal increases in extracellular potassium ion activity (K+o), and anoxia with maximal decreases in tissue oxygen tension (tPO2) and increases in the reduction/oxidation (redox) ratios of the mitochondrial electron transport carriers. Studies were directed toward relationships among these events during cerebral ischemia (“four-vessel occlusion model”) in pentobarbital anesthetized rats. Results demonstrate that EEG suppression and anoxic depolarization do not occur as a simple function of progressive oxygen decline during cerebral ischemia. Rates of K+ elevation, tPO2 decline, and cytochrome a,a3 reduction were decreased in the immediate period following EEG suppression. Latency to EEG suppression was inversely correlated with latency to maximal cytochrome reduction. In contrast, AD was associated with increased rates of tPO2 decline and cytochrome a,a3 reduction. Latency to AD was related to latency of subsequent maximal cytochrome a,a3 reduction. These data suggest that EEG suppression spares oxygen while AD accelerates the progression to energy failure by accelerating the decline in oxygen stores in brain following global ischemia.

Role of adenosine in hypoxic alterations of anaphylaxis of isolated guinea pig hearts

1989 ◽  
Vol 257 (5) ◽  
pp. H1378-H1388
Author(s):  
L. J. Heller ◽  
G. J. Trachte ◽  
J. F. Regal
Keyword(s):  
Guinea Pig ◽  
Vascular Resistance ◽  
Adenosine Receptor ◽  
Guinea Pigs ◽  
Adenosine Release ◽  
Adenosine Receptor Antagonist ◽  
Isolated Hearts ◽  
Hypoxic Conditions ◽  
Intracardiac Injection

Previous studies suggest that high levels of adenosine may enhance histamine release and contribute to atrioventricular (AV) nodal conduction arrhythmias during anaphylaxis of isolated guinea pig hearts. To determine whether elevations in endogenous adenosine evoked by hypoxic conditions have similar effects, isolated hearts of guinea pigs passively sensitized by intracardiac injection were perfused with solutions equilibrated with 95% O2 (normoxia) or 30% O2 (hypoxia). When compared with normoxia, hypoxia before antigen challenge increased adenosine release, decreased vascular resistance, and prolonged P-R intervals, whereas hypoxia during anaphylaxis potentiated the increase in adenosine release, attenuated the increases in vascular resistance and atrial rate, and increased the occurrence of conduction arrhythmias without altering the antigen-induced release of either histamine or thromboxane. Addition of the adenosine receptor antagonist 8-(4-sulfophenyl)theophylline (SP-T) to the hypoxic perfusate significantly decreased antigen-induced release of histamine and thromboxane. These data indicate that 1) hypoxia-induced depression of antigen-induced mediator release may be counteracted by the stimulatory effect of the increased adenosine induced by hypoxia, and 2) under hypoxic conditions, adenosine's negative dromotropic, chronotropic, and vasodilatory effects may influence the anaphylactic reaction.

CPX, a selective A1-adenosine-receptor antagonist, regulates intracellular pH in cystic fibrosis cells

1995 ◽  
Vol 269 (1) ◽  
pp. C226-C233 ◽  
Author(s):  
V. Casavola ◽  
R. J. Turner ◽  
C. Guay-Broder ◽  
K. A. Jacobson ◽  
O. Eidelman ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Receptor Antagonist ◽  
Intracellular Ph ◽  
Adenosine Receptor ◽  
Ph Regulation ◽  
Cystic Fibrosis Transmembrane Regulator ◽  
Wild Type ◽  
A1 Adenosine Receptor ◽  
Adenosine Receptor Antagonist ◽  
Cystic Fibrosis Transmembrane

The selective A1-adenosine-receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (CPX), has been reported to activate Cl- efflux from cystic fibrosis cells, such as pancreatic CFPAC-1 and lung IB3 cells bearing the cystic fibrosis transmembrane regulator(delta F508) mutation, but has little effect on the same process in cells repaired by transfection with wild-type cystic fibrosis transmembrane regulator (O. Eidelman, C. Guay-Broder, P. J. M. van Galen, K. A. Jacobson, C. Fox, R. J. Turner, Z. I. Cabantchik, and H. B. Pollard. Proc. Natl. Acad. Sci. USA 89: 5562-5566, 1992). We report here that CPX downregulates Na+/H+ exchange activity in CFPAC-1 cells but has a much smaller effect on cells repaired with the wild-type gene. CPX also mildly decreases resting intracellular pH. In CFPAC-1 cells, this downregulation is dependent on the presence of adenosine, since pretreatment of the cells with adenosine deaminase blocks the CPX effect. We also show that, by contrast, CPX action on these cells does not lead to alterations in intracellular free Ca2+ concentration. We conclude that CPX affects pH regulation in CFPAC-1 cells, probably by antagonizing the tonic action of endogenous adenosine.

Acute elevation of plasma non-esterified fatty acids increases pulse wave velocity and induces peripheral vasodilation in humans in vivo

2007 ◽  
Vol 113 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Niels P. Riksen ◽  
Marlies Bosselaar ◽  
Stephan J.L. Bakker ◽  
Robert J. Heine ◽  
Gerard A. Rongen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Pulse Wave Velocity ◽  
Wave Velocity ◽  
Adenosine Receptor ◽  
Pulse Wave ◽  
Adenosine Receptor Antagonist ◽  
Sympathetic Nervous ◽  
Control Infusion

Plasma NEFA (non-esterified fatty acid) concentrations are elevated in patients with obesity. In the present study we first aimed to provide an integral haemodynamic profile of elevated plasma NEFAs by the simultaneous assessment of blood pressure, pulse wave velocity, FBF (forearm blood flow) and sympathetic nervous system activity during acute elevation of NEFAs. Secondly, we hypothesized that NEFA-induced vasodilation is mediated by adenosine receptor stimulation. In a randomized cross-over trial in healthy subjects, Intralipid® was infused for 2 h to elevate plasma NEFAs. Glycerol was administered as the Control infusion. We assessed blood pressure, pulse wave velocity, FBF (using venous occlusion plethysmography) and sympathetic nervous system activity by measurement of noradrenaline and adrenaline. During the last 15 min of Intralipid®/Control infusion, the adenosine receptor antagonist caffeine (90 μg·min−1·dl−1) was administered into the brachial artery of the non-dominant arm. Compared with Control infusion, Intralipid® increased pulse wave velocity, SBP (systolic blood pressure) and pulse pressure, as well as FBF (from 1.8±0.2 to 2.7±0.6 and from 2.3±0.2 to 2.7±0.6 ml·min−1·dl−1 for Intralipid® compared with Control infusion; P<0.05, n=9). Although in a positive control study caffeine attenuated adenosine-induced forearm vasodilation (P<0.01, n=6), caffeine had no effect on Intralipid®-induced vasodilation (P=0.5). In conclusion, elevation of plasma NEFA levels increased pulse wave velocity, SBP and pulse pressure. FBF was also increased, either by baroreflex-mediated inhibition of the sympathetic nervous system or by a direct vasodilating effect of NEFAs. As the adenosine receptor antagonist caffeine could not antagonize the vasodilator response, this response is not mediated by adenosine receptor stimulation.

Synthesis of an o-Nitrobenzyl Attached A1 Adenosine Receptor Antagonist, a Prodrug Approach.

ChemInform ◽  
2003 ◽  
Vol 34 (47) ◽  
Author(s):  
HeXi Chang ◽  
Carol Ensinger ◽  
Robert D. McCargar ◽  
Bruno M. Vittimberga
Keyword(s):  
Receptor Antagonist ◽  
Adenosine Receptor ◽  
A1 Adenosine Receptor ◽  
Adenosine Receptor Antagonist
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