scholarly journals Heterologous desensitization of the cyclic AMP-independent glycogenolytic response in rat liver cells

1981 ◽  
Vol 200 (3) ◽  
pp. 509-514 ◽  
Author(s):  
B Bréant ◽  
S Keppens ◽  
H De Wulf

Vasopressin and alpha-adrenergic agonists are known to be potent cyclic AMP-independent Ca2+-dependent activators of liver glycogen phosphorylase. When hepatocytes are pre-incubated with increasing concentrations of vasopressin or of the alpha-agonist phenylephrine, they become progressively unresponsive to a second addition of the respective agonist. The relative abilities of six vasopressin analogues and of five alpha-agonists to activate glycogen phosphorylase and to cause subsequent desensitization are highly correlated, indicating that the same vasopressin and alpha-adrenergic receptors are involved in both responses. About 5-times-higher peptide concentrations are needed to desensitize the cells than to activate their glycogen phosphorylase, whereas the concentrations of alpha-agonists required for the desensitization are only twice those needed for the activation of phosphorylase. The desensitization is not mediated by a perturbation in the agonist-receptor interaction. It is clearly heterologous, i.e. it is not agonist-specific, and must therefore involve a mechanism common to both series of agonists. The evidence for a role of Ca2+ movements or phosphatidylinositol turnover is briefly discussed.

1981 ◽  
Vol 240 (3) ◽  
pp. E226-E232
Author(s):  
K. A. Freude ◽  
L. S. Sandler ◽  
F. J. Zieve

To examine the role of ionic factors in the regulation of glycogen metabolism, we examined the effects of electrical stimulation on liver glycogen cycle enzymes. Passage of electric current through a suspension of rat hepatocytes caused the conversion of glycogen phosphorylase to its active (a) form and the simultaneous conversion of glycogen synthase to its inactive (D) form. The rise in phosphorylase a activity was dependent on the magnitude of current flow, was detectable after 5 s of current flow, and was rapidly reversible on cessation of stimulation. The activation of phosphorylase by shocking was completely eliminated by depletion of cellular Ca2+ and was restored by readdition of Ca2+. Cyclic AMP and cyclic GMP levels were unaffected by shocking. It is concluded that shocking, in the absence of any hormone or exogenous chemical, causes an increase in cytosol Ca2+, which in turn leads to activation of phosphorylase and inactivation of synthase. Electrical stimulation may serve as a model system for studying the role of ions in metabolic regulation.


1985 ◽  
Vol 231 (3) ◽  
pp. 797-799 ◽  
Author(s):  
S Keppens ◽  
H De Wulf

Purinergic agonists cause a dose-dependent activation of glycogen phosphorylase in isolated rat hepatocytes. Half-maximally effective concentrations are 5 × 10(-7)M for ATP, 2 × 10(-6)M for ADP, and about 5 × 10(-5) M for AMP and adenosine. This potency series indicates the presence of P2-purinergic receptors. The mode of action of ATP appears to be identical with that of the Ca2+-dependent glycogenolytic hormones angiotensin, vasopressin and alpha 1-adrenergic agonists. (1) They all require Ca2+ for phosphorylase activation; (2) they do not increase cyclic AMP levels; (3) they are susceptible to heterologous desensitization by vasopressin and phenylephrine; (4) they lower cyclic AMP concentrations in hepatocytes stimulated by glucagon, most probably mediated by an enhanced phosphodiesterase activity.


1977 ◽  
Vol 55 (8) ◽  
pp. 1297-1303 ◽  
Author(s):  
R. M. Walker ◽  
P. H. Johansen

The role of the pituitary gland in goldfish liver carbohydrate metabolism was studied by examining the effects of its removal on the livers of starved animals and on glycogenolytic enzymes.Five weeks starvation after hypophysectomy or sham operation resulted in significantly lower total liver glycogen levels compared with respective fed controls. The larger liver glycogen reserves of starved hypophysectomized fish than fed, sham-operated animals indicate gluconeogenesis is operating to produce glycogen.Glucose-6-phosphatase (EC 3.1.3.9) and glycogen phosphorylase (EC 2.4.1.1) were assayed in liver supernatant fractions from hypophysectomized and sham-operated goldfish. Hypophysectomy resulted in an apparent decline in the activity of glucose-6-phosphatase, but no change in glycogen phosphorylase, compared with sham-operated controls. Reduced glucose-6-phosphatase activity is consistent with lowered glycogenolysis as a cause of liver glycogen accumulation in hypophysectomized goldfish. It is suggested that reduced glycogenolysis could be related to reduced peripheral use of carbohydrate. The possible role of ACTH and glucocorticoids is discussed.


1995 ◽  
Vol 74 (05) ◽  
pp. 1323-1328 ◽  
Author(s):  
Dominique Lasne ◽  
José Donato ◽  
Hervé Falet ◽  
Francine Rendu

SummarySynthetic peptides (TRAP or Thrombin Receptor Activating Peptide) corresponding to at least the first five aminoacids of the new N-terminal tail generated after thrombin proteolysis of its receptor are effective to mimic thrombin. We have studied two different TRAPs (SFLLR, and SFLLRN) in their effectiveness to induce the different platelet responses in comparison with thrombin. Using Indo-1/AM- labelled platelets, the maximum rise in cytoplasmic ionized calcium was lower with TRAPs than with thrombin. At threshold concentrations allowing maximal aggregation (50 μM SFLLR, 5 μM SFLLRN and 1 nM thrombin) the TRAPs-induced release reaction was about the same level as with thrombin, except when external calcium was removed by addition of 1 mM EDTA. In these conditions, the dense granule release induced by TRAPs was reduced by over 60%, that of lysosome release by 75%, compared to only 15% of reduction in the presence of thrombin. Thus calcium influx was more important for TRAPs-induced release than for thrombin-induced release. At strong concentrations giving maximal aggregation and release in the absence of secondary mediators (by pretreatment with ADP scavengers plus aspirin), SFLLRN mobilized less calcium, with a fast return towards the basal level and induced smaller lysosome release than did thrombin. The results further demonstrate the essential role of external calcium in triggering sustained and full platelet responses, and emphasize the major difference between TRAP and thrombin in mobilizing [Ca2+]j. Thus, apart from the proteolysis of the seven transmembrane receptor, another thrombin binding site or thrombin receptor interaction is required to obtain full and complete responses.


1994 ◽  
Vol 30 (10) ◽  
pp. 213-219 ◽  
Author(s):  
Hendrik Pieters ◽  
Victor Geuke

Samples of yellow eel from various locations in the Dutch Rhine area have been analyzed for trend monitoring of mercury since 1977. In the western Rhine delta mercury levels in eels have hardly changed since the seventies, whereas in the eastern part of the Dutch Rhine area a considerable decrease of mercury concentrations in eel has occurred. Because of continuous sedimentation of contaminated suspended matter transported from upstream regions, accumulation rates and concentrations of mercury in eel in the western Rhine delta remained at a relatively high level. Analyses of methyl mercury in biota have been performed to elucidate the role of methyl mercury in the mercury contamination of the Dutch Rhine ecosystem. Low percentages of methyl mercury were observed in zooplankton (3 to 35%). In benthic organisms (mussels) percentages of methyl mercury ranged from 30 to 57%, while in fish species and liver of aquatic top predator birds almost all the mercury was present in the form of methyl mercury (> 80%). During the period 1970-1990 mercury concentrations of suspended matter in the eastern Rhine delta have drastically decreased. These concentrations seemed to be highly correlated with mercury concentrations of eel (R = 0.84). The consequences of this relation are discussed.


1993 ◽  
Vol 4 (6) ◽  
pp. 204-209 ◽  
Author(s):  
Wolfgang Schmid ◽  
Doris Nitsch ◽  
Michael Boshart ◽  
Günther Schütz

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