scholarly journals Hepatocyte heterogeneity in response to extracellular adenosine

1993 ◽  
Vol 293 (2) ◽  
pp. 573-581 ◽  
Author(s):  
Y Morimoto ◽  
M Wettstein ◽  
D Häussinger
Keyword(s):  
Perfusion Pressure ◽  
Thromboxane B2 ◽  
Prostaglandin D2 ◽  
Extracellular Adenosine ◽  
Single Pass ◽  
Prostaglandin Release ◽  
Adenosine Concentration ◽  
Hepatocyte Heterogeneity ◽  
Glucose Output ◽  
Eicosanoid Formation

Metabolic and haemodynamic effects of adenosine were studied in antegrade and retrograde rat liver perfusions with influent nucleoside concentrations either below (i.e. 20 microM) or exceeding (i.e. 200-300 microM) the single-pass clearance capacity of the liver. Adenosine (20 microM) increased in antegrade perfusions the perfusion pressure and markedly stimulated prostaglandin D2, thromboxane B2 and glucose output, whereas in retrograde perfusions no pressure and eicosanoid response occurred and glucose output was stimulated only slightly. The perfusion-direction-dependent differences in the glucose and pressure response to adenosine (20 microM) were fully abolished in presence of ibuprofen (50 microM). When the adenosine concentration in influent was raised to 200-300 microM, i.e. to a concentration exceeding single-pass clearance of the nucleoside, the adenosine-induced prostaglandin D2 release was about 10-fold higher in retrograde perfusions than in antegrade perfusions. On the other hand, both adenosine (20-300 microM)-induced cyclic AMP (cAMP) and K+ release from the liver were not affected by the direction of perfusion, and maximal effects on cAMP release were observed at influent adenosine concentrations of 100 microM. The basal rate (adenosine absent) of prostaglandin D2 and thromboxane B2 release was about 10-fold higher in retrograde than in antegrade perfusion experiments, whereas the basal cAMP release from the liver was not affected by the direction of perfusion. Maximal adenosine-stimulated glucose output was significantly higher in antegrade than in retrograde perfusions at all adenosine concentrations tested (range 10-300 microM). Ibuprofen abolished this difference, indicating that eicosanoids liberated under the influence of adenosine contribute to the glycogenolytic response in antegrade, but not in retrograde, perfusion. Desensitization occurred following repetitive adenosine infusion; this was more pronounced for adenosine-induced prostaglandin release than for cAMP or K+ efflux. The data suggest the following. (i) Both cAMP and eicosanoids are involved in the stimulation of glycogenolysis by adenosine. (ii) Eicosanoids are probably liberated under the influence of extracellular adenosine from a portal pre-sinusoidal compartment and accordingly stimulate glycogenolysis only in antegrade perfusions. Thus signals derived from portal vein structures can modulate hepatocellular function. (iii) Contractile elements are probably located also inside the liver acinus. (iv) Eicosanoids released into the hepatic vein reflect less than 10% of hepatic eicosanoid formation, because of marked clearance by perivenous hepatocytes.

scholarly journals Stimulation of release of prostaglandin D2 and thromboxane B2 from perfused rat liver by extracellular adenosine

1990 ◽  
Vol 270 (1) ◽  
pp. 39-44 ◽  
Author(s):  
S vom Dahl ◽  
M Wettstein ◽  
W Gerok ◽  
D Häussinger
Keyword(s):  
Rat Liver ◽  
Portal Pressure ◽  
Thromboxane B2 ◽  
Adenosine Infusion ◽  
Isolated Perfused Rat Liver ◽  
Signal Molecules ◽  
Prostaglandin D2 ◽  
Perfused Rat Liver ◽  
Glucose Output ◽  
Stimulation Of

In isolated perfused rat liver, adenosine infusion (50 microM) led to increases in glucose output and portal pressure and a net K+ release of 3.7 +/- 0.21 mumol/g, which was followed by an equivalent net K+ uptake after cessation of the nucleoside infusion. These effects were accompanied by a transient stimulation of hepatic prostaglandin D2 and thromboxane B2 release. The Ca2+ release observed upon adenosine infusion (50 microM) was 23.5 +/- 5.2 nmol/g, i.e. 10-20% of the Ca2+ release observed with extracellular ATP (50 microM). Indomethacin (10 microM) prevented the adenosine-induced stimulation of glucose output and the increase in portal pressure by 79 and 63% respectively, and completely abolished the stimulation of prostaglandin D2 release. The thromboxane A2 receptor antagonist BM 13.177 (20 microM), the phospholipase A2 inhibitor 4-bromophenacyl bromide (20 microM) and the cyclo-oxygenase inhibitor ibuprofen (50 microM) also decreased the glycogenolytic and vasoconstrictive responses of the perfused rat liver upon adenosine infusion by 50-80%. When the indomethacin inhibition of adenosine-induced prostaglandin D2 release was titrated, a close correlation between prostaglandin D2 release and the metabolic and vascular responses to adenosine was observed. These findings suggest an important role for eicosanoids in mediating the nucleoside responses in the perfused rat liver. Since eicosanoids are known to be formed by non-parenchymal cells in rat liver [Decker (1985) Semin. Liver Dis. 5, 175-190], the present study gives further evidence for an important role of eicosanoids as signal molecules between the different liver cell populations.

scholarly journals Melittin stimulates liver glycogenolysis and the release of prostaglandin D2 and thromboxane B2

1990 ◽  
Vol 269 (1) ◽  
pp. 273-275 ◽  
Author(s):  
J A García-Sáinz ◽  
S M T Hernández-Sotomayor ◽  
M Macías-Silva
Keyword(s):  
Rat Liver ◽  
Thromboxane B2 ◽  
Prostaglandin D2 ◽  
Perfused Rat Liver ◽  
Initial Burst ◽  
Glucose Output ◽  
Liver Glycogenolysis ◽  
Stimulation Of

Melittin stimulates glycogenolysis and induces vasoconstriction in perfused rat liver. The effect was rapid and associated with production and release of prostaglandin D2 and thromboxane B2. Indomethacin blocked the release of these eicosanoids and the stimulation of glycogenolysis induced by melittin. Ibuprofen blocked the release of prostaglandin D2 induced by melittin and markedly attenuated that of thromboxane B2. Interestingly, the initial burst of glucose output induced by melittin was not inhibited by ibuprofen, although the duration of the glycogenolytic action of the peptide was greatly diminished.

Survival of energy failure in the anoxic frog brain: delayed release of glutamate.

1997 ◽  
Vol 200 (22) ◽  
pp. 2913-2917 ◽  
Author(s):  
P L Lutz ◽  
R Reiners
Keyword(s):  
Neurotransmitter Release ◽  
Energy Charge ◽  
Atp Depletion ◽  
Extracellular Adenosine ◽  
Frog Brain ◽  
Adenosine Concentration ◽  
Excitatory Neurotransmitters ◽  
The Relationship ◽  
Brain Energy ◽  
Energy Failure

This study investigated the relationship between energy failure and neurotransmitter release in the frog (Rana pipiens) brain during 1-3 h of anoxia. Unlike truly anoxia-tolerant species, the frog does not defend its brain energy charge. When exposed to anoxia at 25 degrees C, there is an immediate fall in brain ATP levels, which reach approximately 20% of normoxic levels in approximately 60 min. The frog, nevertheless, survives another 1-2 h of anoxia. At 100 min of anoxia, there is an increase in extracellular adenosine concentration, probably originating from the increased intracellular adenosine concentration caused by the breakdown of intracellular ATP. Increases in the levels of extracellular glutamate and GABA do not occur until 1-2 h after ATP depletion. This response is quite unlike that recorded for other vertebrates, anoxia-tolerant or anoxia-intolerant, where energy failure quickly results in an uncontrolled and neurotoxic release of excitatory neurotransmitters. In the frog, the delay in excitotoxic neurotransmitter release may be one of the factors that allow a period of survival after energy failure. Clearly, energy failure by itself is not a fatal event in the frog brain.

scholarly journals Effects of Pyrazolone Drugs on Synthesis of Prostaglandin D2 and Thromboxane B2 by Platelets

1977 ◽  
Author(s):  
M. Ali ◽  
J. Zamecnik ◽  
J. W. D. McDonald
Keyword(s):  
Mass Spectrometry ◽  
Human Platelets ◽  
Thromboxane B2 ◽  
Gas Chromatography Mass Spectrometry ◽  
Prostaglandin D2 ◽  
Freezing And Thawing ◽  
Plasma Albumin ◽  
Cyclooxygenase Activity ◽  
Silicic Acid Chromatography ◽  
Hydroxylated Fatty Acids

The principle products of arachidonic acid (AA) in platelets are hydroxylated fatty acids and thromboxane B2(TXB2). Prostaglandin D2(PGD2) has been considered to be a nonenzymatic degradation product of prostaglandin H2 formed in the presence of plasma albumin. Using 14C AA as substrate and thin layer and silicic acid chromatography, we have demonstrated PGD2 synthesis by washed (albumin-free) human platelets. The identity of PGD2 was confirmed by gas chromatography-mass spectrometry. In platelets lysed by freezing and thawing synthesis of TXB2 and PGD2 was approximately equal and equally inhibited by pyrazolones.Synthesis of PGD2 by platelets is enzymatic and may contribute to bronchoconstrictor, vasomotor, and inflammatory effects induced by platelet aggregation. Pyrazolones appear to inhibit cyclooxygenase activity rather than the breakdown of cyclic endoperoxides as previously postulated.

Oxygen partial pressure and free intracellular adenosine of isolated cardiomyocytes

1991 ◽  
Vol 260 (4) ◽  
pp. C708-C714 ◽  
Author(s):  
R. T. Smolenski ◽  
J. Schrader ◽  
H. de Groot ◽  
A. Deussen
Keyword(s):  
Oxygen Consumption ◽  
Extracellular Space ◽  
Oxygen Supply ◽  
Oxygen Demand ◽  
Nucleoside Transport ◽  
Isolated Cardiomyocytes ◽  
Homocysteine Thiolactone ◽  
Rat Cardiomyocytes ◽  
Extracellular Adenosine ◽  
Adenosine Concentration

Adenosine formation by the heart is known to critically depend on the ratio of oxygen supply to oxygen demand, but the sensitivity of cardiomyocytes to defined changes in PO2 is not known. Isolated metabolically stable rat cardiomyocytes were incubated up to 45 min at constant PO2 values ranging from 0.1 to 100 mmHg using a feedback-controlled incubation system (oxystat system). Changes of the free intracellular adenosine concentration were measured after trapping of adenosine by cytosolic S-adenosylhomocysteine (SAH) hydrolase in the presence of 200 microM L-homocysteine thiolactone. Rate of SAH formation was constant at a PO2 between 3 and 100 mmHg and gradually increased at PO2 less than 3 mmHg. Cellular ATP decreased only at PO2 less than 1 mmHg, and this was accompanied by a decline of oxygen consumption. Treatment of cells with 5.5 mM deoxyglucose and 4 micrograms/ml oligomycin increased SAH formation 60-fold and was associated with elevated intra- and to a lesser extent extracellular adenosine levels. Inhibition of nucleoside transport with 20 microM S-(p-nitrobenzyl)-6-thioinosine steepened the transmembrane adenosine gradient. Our findings suggest that the cardiomyocyte responds to metabolic poisoning and oxygen deprivation with an enhanced formation of adenosine. This adenosine is mainly formed intracellularly and reaches the extracellular space by diffusion. Threshold for adenosine formation is as low as 3 mmHg.

K+ATP channels and adenosine are not necessary for coronary autoregulation

1997 ◽  
Vol 273 (3) ◽  
pp. H1299-H1308 ◽  
Author(s):  
D. W. Stepp ◽  
K. Kroll ◽  
E. O. Feigl
Keyword(s):  
Carbon Dioxide ◽  
Blood Flow ◽  
Coronary Blood Flow ◽  
Left Main Coronary Artery ◽  
Perfusion Pressure ◽  
Carbon Dioxide Tension ◽  
Coronary Pressure ◽  
Adenosine Concentration ◽  
The Face

Autoregulation is defined as the intrinsic ability of an organ to maintain constant flow in the face of changing perfusion pressure. The present study evaluated the role of several potential mediators of coronary autoregulation: interstitial adenosine, ATP-sensitive K+ (K+ATP) channels, and myocardial oxygen and carbon dioxide tensions as reflected by coronary venous oxygen and carbon dioxide tensions. The left main coronary artery was cannulated, and blood was perfused at controlled pressures in closed-chest dogs. Interstitial adenosine concentration was estimated from arterial and venous adenosine concentrations with a previously described mathematical model. Autoregulation of coronary blood flow was observed between 100 and 60 mmHg. Glibenclamide, an inhibitor of K+ATP channels, reduced coronary blood flow by 19% at each perfusion pressure, but autoregulation was preserved. After stepwise reductions in coronary pressure to values > or = 70 mmHg, adenosine concentrations did not increase above basal levels. Adenosine concentration was elevated at 60 mmHg, suggesting a role for adenosine at the limit of coronary autoregulation. Adenosine is not required because glibenclamide, an inhibitor of adenosine-mediated vasodilation, did not reduce autoregulation or increase adenosine concentration. Coronary venous oxygen and carbon dioxide tensions were little changed during autoregulation before the inhibition of K+ATP channels and adenosine vasodilation with glibenclamide. However, coronary venous carbon dioxide tension rose progressively with decreasing coronary pressure after glibenclamide. The increase in carbon dioxide indirectly suggests that carbon dioxide-mediated vasodilation compensated for the loss of K+ATP-channel function. In summary, neither K+ATP channels nor adenosine is necessary to maintain coronary flow in the autoregulatory range of coronary arterial pressure from 100 to 60 mmHg.

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