scholarly journals Modulation of maximal glycogenolysis in perfused rat liver by adenosine and ATP

1991 ◽  
Vol 277 (3) ◽  
pp. 597-602 ◽  
Author(s):  
F Vanstapel ◽  
M Waebens ◽  
P Van Hecke ◽  
C Decanniere ◽  
W Stalmans
Keyword(s):  
Kinase Inhibitor ◽  
Portal Pressure ◽  
Adenosine Kinase ◽  
Phosphorylase Kinase ◽  
Dibutyryl Cyclic Amp ◽  
Eicosanoid Synthesis ◽  
Biphasic Effect ◽  
Maximal Activation ◽  
P1 Receptor ◽  
Rat Livers

Rat livers perfused at constant flow via the portal vein with dibutyryl cyclic AMP produced glucose equivalents at a steady maximal rate (6 mumol/min per g of liver). Addition of adenosine (150 microM) caused a biphasic effect. (i) First, the glycogenolytic rate rose transiently, to a mean peak of 150% of control levels after 2 min. This glycogenolytic burst was reproduced by two P1-receptor agonists, but not by ATP, and was blocked by a P1-antagonist (8-phenyltheophylline), as well as by inhibitors of eicosanoid synthesis (indomethacin, ibuprofen or aspirin). It did not occur in phosphorylase-kinase-deficient livers. The adenosine-induced glycogenolytic burst coincided with moderate and transient changes in portal pressure (+6 cmH2O) and O2 consumption (-20%), but it could not be explained by an increase in cytosolic Pi, since the n.m.r. signal fell precipitously. (ii) Subsequently, the rate of glycogenolysis decreased to one-third of the preadenosine value, in spite of persistent maximal activation of phosphorylase. The decrease could be linked to the decline in cytosolic Pi: both changes were prevented by the adenosine kinase inhibitor 5-iodotubercidin, whereas they were not affected by ibuprofen or 8-phenyltheophylline, and were not reproduced by non-metabolized adenosine analogues. In comparison with adenosine, ATP caused a slower decrease of Pi and of glycogenolysis. The fate of the cytosolic Pi was unclear, especially with administered ATP, which did not increase the n.m.r.-detectable intracellular ATP.

Analgesic and anti-inflammatory effects of A-286501, a novel orally active adenosine kinase inhibitor

Pain ◽  
2002 ◽  
Vol 96 (1) ◽  
pp. 107-118 ◽  
Author(s):  
Michael F. Jarvis ◽  
Haixia Yu ◽  
Steve McGaraughty ◽  
Carol T. Wismer ◽  
Joe Mikusa ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Adenosine Kinase ◽  
Anti Inflammatory ◽  
Orally Active

Role of protein kinases in regulating sheep erythrocyte K-Cl cotransport

1996 ◽  
Vol 271 (1) ◽  
pp. C255-C263 ◽  
Author(s):  
P. W. Flatman ◽  
N. C. Adragna ◽  
P. K. Lauf
Keyword(s):  
Protein Kinases ◽  
Tyrosine Kinases ◽  
Kinase Inhibitor ◽  
Sheep Erythrocyte ◽  
Inhibition Constant ◽  
Calyculin A ◽  
Sheep Erythrocytes ◽  
A 23187 ◽  
Maximal Activation

K-Cl cotransport in sheep erythrocytes can be activated by treatment either with A-23187 and EDTA to reduce concentration of internal ionized Mg [Mg]i) to submicromolar levels, with staurosporine, a potent kinase inhibitor, or with N-ethylmaleimide (NEM). Activation by these maneuvers is prevented and reversed by genistein [inhibition constant (Ki) of 15 microM], which inhibits tyrosine kinases (TK). The related glycosidated compound genistin, which does not inhibit TK, does not inhibit transport, whereas another TK inhibitor, tyrphostin B46, inhibits both basal and stimulated transport (Ki of 28 microM). Cotransport activation by NEM is prevented and reversed by the phosphatase inhibitor, calyculin A, and activation by staurosporine occurs only if cells contain ATP. Increasing [Mg]i inhibits cotransport in the presence of calyculin A whether or not staurosporine is present as well. Our work suggests that genistein inhibits cotransport through a TK and that staurosporine and NEM activate cotransport, probably through inhibition of other kinases, causing stimulation through dephosphorylation of a protein (possibly the transporter itself) be a serine/threonine phosphatase. [Mg]i inhibits cotransport by activating a kinase (concentration for half-maximal activation of 10 microM) that phosphorylates this protein.

Protective effect of an adenosine kinase inhibitor in septic shock

Resuscitation ◽  
1995 ◽  
Vol 29 (2) ◽  
pp. 180 ◽  
Author(s):  
GS Firestein ◽  
D Boyle ◽  
DA Bullough ◽  
HE Gruber ◽  
FG Sajjadi ◽  
...  
Keyword(s):  
Septic Shock ◽  
Protective Effect ◽  
Kinase Inhibitor ◽  
Adenosine Kinase

Effect of thioridazine and chlorpromazine on rat liver hemodynamics

1960 ◽  
Vol 199 (5) ◽  
pp. 793-796 ◽  
Author(s):  
Gabriel L. Plaa ◽  
Edwin C. McGough ◽  
Gerry J. Blacker ◽  
James M. Fujimoto
Keyword(s):  
Mean Arterial Pressure ◽  
Marked Decrease ◽  
Portal Pressure ◽  
Liver Ischemia ◽  
Phenothiazine Derivatives ◽  
Perfusate Flow ◽  
Flow Through ◽  
Liver Hemodynamics ◽  
Rat Livers ◽  
Higher Doses

Evidence is presented which indicates that two phenothiazine derivatives—thiroidazine and chlorpromazine— increase hepatic vascular resistance in isolated perfused rat livers. These substances produce the following: a) a decrease in perfusate flow through the organ, b) an increase in portal pressure and c) a decrease in organ weight. These effects were demonstrated with doses as low as 4 mg but were quantitatively more pronounced and of longer duration with higher doses. Tachyphylaxis did not occur. The effects could be blocked with sodium nitrite. Both phenothiazines were found to produce liver ischemia in anesthetized, laparotomized rats. Thioridazine was found to raise portal pressure in anesthetized, laparotomized cats in spite of a marked decrease in mean arterial pressure.

Discovery of 4-Amino-5-(3-bromophenyl)-7-(6-morpholino-pyridin- 3-yl)pyrido[2,3-d]pyrimidine, an Orally Active, Non-Nucleoside Adenosine Kinase Inhibitor

2001 ◽  
Vol 44 (13) ◽  
pp. 2133-2138 ◽  
Author(s):  
Chih-Hung Lee ◽  
Meiqun Jiang ◽  
Marlon Cowart ◽  
Greg Gfesser ◽  
Richard Perner ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Adenosine Kinase ◽  
Orally Active

The Effect of GP683, an Adenosine Kinase Inhibitor, on the Desflurane Anesthetic Requirement in Dogs

1997 ◽  
Vol 85 (3) ◽  
pp. 675-680 ◽  
Author(s):  
Baoguo Wang ◽  
Jun Tang ◽  
Paul F. White ◽  
Alan C. Foster ◽  
Heather M. Grettenberger ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Adenosine Kinase ◽  
Anesthetic Requirement

scholarly journals Glycogenolysis in liver of phosphorylase kinase-deficient rats during liver perfusion and ischaemia

1983 ◽  
Vol 214 (2) ◽  
pp. 645-648 ◽  
Author(s):  
G Lutaya ◽  
R J Sharma ◽  
J R Griffiths
Keyword(s):  
Liver Perfusion ◽  
Liver Glycogen ◽  
Alpha Activity ◽  
Transient Increase ◽  
Phosphorylase Kinase ◽  
Phosphorylase Activity ◽  
Main Determinant ◽  
Rat Livers

Liver glycogen degradation and phosphorylase activity were measured in normal and phosphorylase kinase-deficient (gsd/gsd) rats. During perfusion or ischaemia, gsd/gsd-rat livers showed a brisk glycogenolysis. There was also a small (1.9-fold) but significant transient increase in their phosphorylase alpha activity during ischaemia, despite their phosphorylase b kinase deficiency; it seems unlikely, however, that this was the main determinant of the glycogenolysis.

scholarly journals Role of cysteinyl-leukotrienes for portal pressure regulation and liver damage in cholestatic rat livers

2013 ◽  
Vol 93 (12) ◽  
pp. 1288-1294 ◽  
Author(s):  
Mark op den Winkel ◽  
Leonore Gmelin ◽  
Julia Schewe ◽  
Natalie Leistner ◽  
Manfred Bilzer ◽  
...  
Keyword(s):  
Liver Damage ◽  
Portal Pressure ◽  
Pressure Regulation ◽  
Cysteinyl Leukotrienes ◽  
Rat Livers

scholarly journals Homocysteine enhances the inhibitory effect of extracellular adenosine on the synthesis of proteins in isolated rat hepatocytes

1995 ◽  
Vol 310 (3) ◽  
pp. 893-896 ◽  
Author(s):  
S Tinton ◽  
P Buc-Calderon
Keyword(s):  
Protein Synthesis ◽  
Kinase Inhibitor ◽  
Adenine Nucleotides ◽  
Rat Hepatocytes ◽  
Isolated Hepatocytes ◽  
Adenosine Kinase ◽  
Isolated Rat Hepatocytes ◽  
Extracellular Adenosine ◽  
Inhibition Of Protein Synthesis ◽  
Isolated Rat

Previous work has shown that extracellular adenosine inhibits the incorporation of radiolabelled leucine into proteins in isolated rat hepatocytes [Tinton, Lefebvre, Cousin and Buc Calderon (1993) Biochim. Biophys. Acta 1176, 1-6]. In this study, we investigated whether its metabolism into adenine nucleotides, inosine or S-adenosylhomocysteine (AdoHcy) is required to induce such an impairment. Incubation of isolated hepatocytes in the presence of adenosine at 0.5 or 1 mM reduces the synthesis of proteins by about 45% after 120 min of incubation. Such an inhibition occurred without cell lysis and was not modified by adding the adenosine kinase inhibitor 5-iodotubercidin (15 microM) or the adenosine deaminase inhibitor coformycin (0.1 microM). It is therefore unlikely that the anabolic and catabolic pathways of adenosine are involved in the inhibition of protein synthesis. Adenosine (1 mM) increased the level of AdoHcy and S-adenosylmethionine by 20- and 5-fold respectively after 60 min of incubation and reduced the methylation index. These events as well as the inhibition of protein synthesis were strongly enhanced in the presence of L-homocysteine (2 mM). It is therefore concluded that the metabolism of adenosine into AdoHcy, which is known to be a potent inhibitor of cellular methylation reactions, may play an important role in the control of translation.

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