scholarly journals The stimulation of glycogenolysis in isolated hepatocytes by opioid peptides

1985 ◽  
Vol 227 (1) ◽  
pp. 191-197 ◽  
Author(s):  
R P Leach ◽  
E H Allan ◽  
M A Titheradge
Keyword(s):  
Opioid Peptides ◽  
Isolated Hepatocytes ◽  
Aminopeptidase Activity ◽  
Initial Product ◽  
Transient Nature ◽  
Adrenergic Antagonists ◽  
Lactate Formation ◽  
Glucose Output ◽  
Dependent Mechanism ◽  
Stimulation Of

Addition of the opioid peptides, [Leu]enkephalin and [Met]enkephalin, to isolated hepatocytes was shown to produce a stimulation of glycogenolysis comparable with that observed in the presence of maximal concentrations of glucagon, adrenaline or angiotensin. This stimulation was demonstrated to be the result of an activation of phosphorylase by a rapid Ca2+-dependent mechanism and was not decreased by the presence or either alpha- or beta-adrenergic antagonists, although it was dependent on the presence of the N-terminal tyrosine residue in the enkephalin molecule. It is suggested that this may be further evidence for specific opioid receptors in the liver. Addition of [Leu]enkephalin also inhibited lactate formation, indicating that the opioid peptides exert a concerted effect on hepatic carbohydrate metabolism to enhance glucose output. The transient nature of the effect of the enkephalins was shown to be the result of a rapid breakdown of the peptides in the incubation as a result of aminopeptidase activity, the initial product being the inactive des-tyrosine derivative.

scholarly journals The stimulation of glycogenolysis and gluconeogenesis in isolated hepatocytes by opioid peptides

1983 ◽  
Vol 216 (2) ◽  
pp. 507-510 ◽  
Author(s):  
E H Allan ◽  
I C Green ◽  
M A Titheradge
Keyword(s):  
Cyclic Amp ◽  
Opioid Peptides ◽  
Isolated Hepatocytes ◽  
Significant Inhibition ◽  
Leucine Enkephalin ◽  
Opioid Agonists ◽  
Independent Mechanism ◽  
Total Glucose ◽  
Glucose Output ◽  
Stimulation Of

The opioid agonists [leucine]enkephalin, [D-Ala2,D-Leu5]enkephalin and dynorphin-(1-13)-peptide, but not morphine, stimulated the conversion of [2-14C]pyruvate into glucose and glycogenolysis when added directly to isolated hepatocytes. Naloxone produced a small but significant inhibition of both the basal and stimulated rate of incorporation of label into glucose but had no effect on the total glucose output by the cells. The effects of the opioid peptides were mediated by a cyclic AMP-independent mechanism.

scholarly journals The stimulation of glycogenolysis in isolated hepatocytes by opioid peptides

1986 ◽  
Vol 238 (2) ◽  
pp. 531-535 ◽  
Author(s):  
R P Leach ◽  
M A Titheradge
Keyword(s):  
Cyclic Amp ◽  
Opioid Peptides ◽  
Glycogen Phosphorylase ◽  
Glycogen Synthase ◽  
Glycogen Metabolism ◽  
Isolated Hepatocytes ◽  
Dependent Protein ◽  
Simultaneous Decrease ◽  
Glycogen Phosphorylase Activity ◽  
Stimulation Of

The opioid peptides [Leu]enkephalin and dynorphin-(1-13) were shown to enhance glycogen breakdown when added directly to hepatocytes. This was the result of a concerted effect on the enzymes of glycogen metabolism, with a stimulation of glycogen phosphorylase activity and a simultaneous decrease in glycogen synthase I activity. The latter only became significant when the enzyme was activated by incubating the cells in presence of 20 mM- or 40 mM-glucose. The effect of the opioid peptides was independent of an increase in cyclic AMP or any change in the activity ratio of the cyclic AMP-dependent protein kinase and was abolished by depleting the cells of Ca2+. Both [Leu]enkephalin and dynorphin-(1-13) produced a significant decrease in cyclic AMP formation, suggesting that in liver, as in neuronal tissue, they may act by inhibiting adenylate cyclase activity.

scholarly journals Pancreastatin activates protein kinase C by stimulating the formation of 1,2-diacylglycerol in rat hepatocytes

1994 ◽  
Vol 303 (1) ◽  
pp. 51-54 ◽  
Author(s):  
V Sánchez-Margalet ◽  
M Lucas ◽  
R Goberna
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Pertussis Toxin ◽  
Time Course ◽  
Rat Hepatocytes ◽  
Isolated Hepatocytes ◽  
Dependent Manner ◽  
Kinase C ◽  
Glucose Output ◽  
Stimulation Of

We describe here the stimulation by pancreastatin of 1,2-diacylglycerol production and protein kinase C activity in liver plasma membrane and isolated hepatocytes. The dose-dependency for the stimulation of both processes was similar to the recently described pattern of glucose output and cytosolic Ca2+ transients produced by pancreastatin. The time course of diacylglycerol production at 30 degrees C showed a rapid increase within 5 min, reaching a maximum at 10 min. Protein kinase C from hepatocytes was dependent on Ca2+ and phosphatidylserine. Neither the pancreastatin-stimulated diacylglycerol production nor the activation of protein kinase C was affected by pretreatment with pertussis toxin. However, the presence of GTP partially inhibited this pancreastatin stimulation of 1,2-diacylglycerol in a dose-dependent manner, although GTP alone stimulates diacylglycerol accumulation. This inhibitory effect of GTP on pancreastatin stimulation of diacylglycerol synthesis was completely abolished by the pretreatment with pertussis toxin. In conclusion, this study provides evidence that pancreastatin stimulates the formation of 1,2-diacylglycerol by a pertussis-toxin-independent mechanism, which may be responsible for the pancreastatin activation of protein kinase C.

Alleviation of pain and depression by specific neural transplants: Fine structural correlates

1992 ◽  
Vol 50 (2) ◽  
pp. 1066-1067
Author(s):  
George D. Pappas ◽  
Jacqueline Sagen
Keyword(s):  
Opioid Peptides ◽  
Chromaffin Cells ◽  
Pain Sensitivity ◽  
Opioid Peptide ◽  
Local Source ◽  
Pain Models ◽  
Neural Transplants ◽  
Adrenergic Antagonists ◽  
Csf Levels ◽  
Donor Source

We have been interested in the use of neural transplants mainly as a local source of neuroactive substances, rather than as a replacement for damaged neural circuities. In particular, we have been exploring the possibilities of reducing pain by transplants of opioid peptide producing cells, and reducing depression by transplants of monoamine-producing cells. For the past several years, work in our laboratory has demonstrated in both acute and chronic pain models that transplantation of adrenal medullary tissue or isolated chromaffin cells into CNS pain modulatory regions can reduce pain sensitivity in rodents. Chromaffin cells were chosen as donor source since they produce high levels of both opioid peptides and catecholamines, substances which independently, and probably synergistically, reduce pain sensitivity when injected locally into the spinal cord. The analgesia produced by these transplants most likely results from the release of both opioid peptides and catecholamines, since it can be blocked or attenuated by opiate or adrenergic antagonists, respectively. Furthermore, CSF levels of met-enkephalin and catecholamines are increased by the transplants.

ANTAGONISM BETWEEN INSULIN AND SELECTIVE ADRENERGIC AGONISTS ON THE GLYCOGEN SYNTHETASE AND PHOSPHORYLASE SYSTEMS OF THE ISOLATED RAT DIAPHRAGM

1975 ◽  
Vol 78 (2) ◽  
pp. 392-400
Author(s):  
Arne T. Hostmark ◽  
Ole Grønnerød ◽  
Robert S. Horn
Keyword(s):  
Glycogen Metabolism ◽  
Rat Diaphragm ◽  
Adrenergic Agonists ◽  
Adrenergic Stimulation ◽  
Insulin Effect ◽  
Glycogen Synthetase ◽  
Adrenergic Antagonists ◽  
Fasted Rats ◽  
Isolated Rat ◽  
Stimulation Of

ABSTRACT The antagonism between insulin and selective adrenergic stimulation on the converting systems for glycogen synthetase and phosphorylase has been investigated in the isolated rat diaphragm. Insulin significantly inhibited stimulation by terbutaline and noradrenaline of phosphorylase b to a conversion as well as stimulation of glycogen synthetase I to D conversion by these agents. The inhibition by insulin was stronger on the synthetase system than on the phosphorylase system. The insulin effect was not dependent upon the presence of glucose. In diaphragms from 24 h fasted rats the response of the phosphorylase system to both agonists decreased. Inhibition by insulin of terbutaline stimulated phosphorylase conversion was maintained upon fasting while no effect of insulin against stimulation by noradrenaline could be obtained in diaphragms from fasted rats. The effects of fasting and insulin were not influenced by beta adrenergic antagonists (practolol and butoxamine). The results indicate a difference in sensitivity of the synthetase and phosphorylase systems to insulin and suggest that noradrenaline and terbutaline influence glycogen metabolism by differing mechanisms.

scholarly journals Regulation of mitochondrial pyruvate carboxylation in isolated hepatocytes by acute insulin treatment

1983 ◽  
Vol 214 (2) ◽  
pp. 451-458 ◽  
Author(s):  
A B Chisholm ◽  
E H Allan ◽  
M A Titheradge
Keyword(s):  
Insulin Treatment ◽  
Second Messengers ◽  
Isolated Hepatocytes ◽  
Carboxylase Activity ◽  
Effector Molecules ◽  
Pyruvate Carboxylation ◽  
Isolated Mitochondria ◽  
Glucose Synthesis ◽  
Important Site ◽  
Stimulation Of

The effect of acute insulin treatment of hepatocytes on pyruvate carboxylation in both isolated mitochondria and cells rendered permeable by filipin was examined. Challenging the cells with insulin alone had no effect on either the basal rate of pyruvate carboxylation or gluconeogenesis, although it did suppress the responses to both glucagon and catecholamines. Insulin treatment was unable to antagonize the enhanced rate of pyruvate carboxylation caused by stimulation of the cells with either angiotensin or vasopressin. Neither insulin nor the gluconeogenic hormones altered the total extractable pyruvate carboxylase activity in the isolated mitochondria, suggesting that the effect of hormones at the level of the isolated intact organelle was mediated via alterations in the intramitochondrial concentrations of effector molecules, notably ATP and the [ATP]/[ADP] ratio and substrate availability. The alterations in pyruvate carboxylation correlate well with glucose synthesis in terms of sensitivity to effector molecules, putative second messengers and time of onset of the response, indicating that alterations in the flux through this enzyme are compatible with it being an important site in the control of gluconeogenesis from C3 precursors.

Glucagon as a myocardial stimulant

1970 ◽  
Vol 8 (20) ◽  
pp. 77-79
Keyword(s):  
Pancreatic Islets ◽  
Heart Muscle ◽  
Physiological Effect ◽  
Inotropic Effect ◽  
Single Chain ◽  
Glucose Output ◽  
Stimulation Of

Glucagon is a polypeptide secreted by the α -cells of the pancreatic islets; it consists of 29 aminoacids arranged in a single chain. Its most important physiological effect is probably the stimulation of glucose output from the liver, but at concentrations higher than those found physiologically, glucagon increases the contractility of heart muscle as do the catecholamines. This inotropic effect of glucagon may therefore find a new role in therapeutics.

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