Liver 3': 5'-Nucleotide Phosphodiesterase and its Activity in Rat Livers Perfused with Insulin

Menahan, Lawrence A.; Hepp, K.; Wieland, O.

doi:10.1111/j.1432-1033.1969.tb00546.x

Cited by 72 publications

(26 citation statements)

References 27 publications

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“…I n comparison with the total homogenate, a six-fold increase in specific enzyme activity was observed. I n spite of the extensive washing, a residual phosphodiesterase activity remained with this particle preparation which corresponded with specific activities of particulate fractions of rat liver as shown in an earlier report from this laboratory [14]. I n order to prevent breakdown of labeled Ado-3':5'-P in the reaction, theophylline, or the better soluble aminophylline were added to the incubation system at concentrations of 10 and 20 mM, respectively.…”

Section: Studies On the Assay Systemsupporting

confidence: 60%

“…The particle preparation employed in the present work was therefore chosen to comprise most of the particulate material of the liver after washing away the soluble protein which contains most of the phosphodiesterase activity [14]. Preliminary studies of different homogenization techniques and different buffers showed the highest yield in adenyl cyclase activity after high speed mechanical homogenization in 0.2 M Tris-C1 at pH 7.4.…”

Section: Studies On the Assay Systemmentioning

confidence: 99%

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Hormone Action on Liver Adenyl Cyclase Activity

Hepp

Edel

Wieland

1970

European Journal of Biochemistry

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Adenyl cyclase activity was measured by conversion of [32P]ATP to adenosine 3′:5′‐cyclic [32P]phosphate in a washed particle suspension from mouse and rat liver. The test contained an ATP regenerating system and 10 mM unlabeled Ado‐3′:5′‐P to trap the labeled Ado‐3′:5′‐P formed. Decreased activities were observed when methyl xanthines were used in place of unlabeled Ado‐3′:5′‐P. The reaction was stimulated by Mg++ which increased Vmax without changing the apparent Km towards ATP. Adenyl cyclase activity was stimulated by synthetic glucagon over the range of 0.1–20 μg/ml. Removal of Ca++ by ethylene glycol‐bis‐(β‐amino‐ethyl ether)‐N,N'‐tetraacetic acid (EGTA) strongly augmented glucagon action, while 1 mM Ca++ was inhibitory. The data suggest enhanced transmission of the hormone signal from the (hypothetical) receptor to the catalytic enzyme unit by chelation of membrane bound calcium. In contrast to the hyperbolic dose response curve observed with glucagon, the curve with fluoride (1–10 mM) was sigmoidal in shape, the effect being inhibited by 1 mM pyrophosphate. Although inhibition by Ca++ was observed, EGTA did not augment the effect of fluoride. The effects of fluoride and glucagon at maximal concentrations were not additive, indicating stimulation of the same adenyl cyclase system.

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Section: Studies On the Assay Systemsupporting

confidence: 60%

Section: Studies On the Assay Systemmentioning

confidence: 99%

Hormone Action on Liver Adenyl Cyclase Activity

Hepp

Edel

Wieland

1970

European Journal of Biochemistry

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“…The increase in cAMP1 is prevented by the acidification induced by acid-loading or amiloride treatment, suggesting that pHi modulates the activity of enzymes involved in cAMP formation [33,34]. Reynolds & Haugaard [35] reported that extractable phosphorylase activity in rat liver slices is significantly increased when external pH is 7.8.…”

Section: Effect Of Heat On Phosphodiesterasementioning

confidence: 99%

Heat treatment induces an increase in intracellular cyclic AMP content in human epidermoid A-431 cells

Kiang

Wu²,

Lin³

1991

Biochemical Journal

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is 2086 + 139 fmol/106 cells. When cells are exposed to 45°C for 10 min, cAMPi increases by 40 +40%, and then returns to basal levels within 30 min. Incubating cells in Ca2+-free or Mg2+-free Hanks solution has no effect on the heat-induced increase in cAMPi, but the increase is inhibited by acid-loading cells to intracellular pH 7.0 or 6.8. In unheated cells, cAMPi increases by 16 + 8 %, 53 + 7 %, or 39 + 8 % when incubated with 3-isobutyl-1-methylxanthine (1 mM), Ro 20-1724 (0.5 mM), or theophylline (1 mM) respectively. However, heat treatment further elevates cAMP1 in cells treated with phosphodiesterase inhibitors, indicating that heat treatment and phosphodiesterase inhibitors elevate cAMPi by a different pathway(s). Heat treatment increases adenylate cyclase activity 2.5-fold. When forskolin (150 IsM), an adenylate cyclase stimulator, is applied to cells, the basal cAMP1 increases 28 + 6-fold compared with controls. Subsequent heating of these cells lowers cAMPi levels to 7.0 + 0.5 times that in control cells. This decrease is prevented by pretreatment with pertussis toxin (30 ng/ml, 24 h), suggesting that G-proteins are involved in the process of heat-induced cAMP1 increase.2-Deoxy-D-glucose (10 mM), NaN3 (10 mM) and 2,4-dinitrophenol (1 mM) also increase cAMPi in A-431 cells. However, application of these metabolic inhibitors to cells before heat treatment does not result in cAMP1 levels greater than that observed in cells with heat alone. Similar observations are obtained in heat-treated cells previously exposed to adenosine, but not to AMP or ADP. These data are the first to suggest that thermally induced increase in cAMP. is due to a combination of activation of adenylate cyclase and G-proteins, and an increase in adenosine owing to ATP breakdown caused by hyperthermia.

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“…The present study indicates that Bu,Ado-3': 5'-P addition to the perfusion medium results in an increased endogenous urea, glucose and ketone body production in the isolated, perfused liver from fasted rats. The choice of Bu2Ado-3':5'-P instead of Ado-3' :5'-P as effector was based on the thinking that the derivative penetrates cell membranes more readily [24] and that it is more resistant to action of phosphodiesterase than Ado-3' :5'-P [24,25,. Levine [45] found that Bu,Ado-3' : 5'-P induces a three-fold greater glycogenolytic effect than the parent Ado-3': 5'-P compound in isolated, perfused liver.…”

Section: Effects Of Insulin and Buado-3' :5'-p On Endogenous Liver Mmentioning

confidence: 99%

“…An increase in phosphodiesterase activity in liver and muscle in vivo was observed by Schultz, Senft and Munske [65] following insulin administration to alloxan-diabetic rats. However, a lack of effect of insulin in vitro or in vivo on the activity of phosphodiesterase has been observed for the rat liver [25,66] and adipose tissue enzyme [48,66,67]. Although after incubation of the tissue with hormone a decrease in cyclase activity has been observed by prior incubation [68], a direct effect of insulin on this enzyme in adipose tissue homogenate is lacking [68,69].…”

Section: Effects Of Insulin and Buado-3' :5'-p On Endogenous Liver Mmentioning

confidence: 99%

Interactions of Glucagon and Insulin on the Metabolism of Perfused Livers from Fasted Rats

Menahan

Wieland²

1969

European Journal of Biochemistry

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Glucagon (28 nM) stimulated gluconeogenesis, urea production and ketogenesis in perfused livers from fasted rats. Since the livers were perfused without added substrate, liver protein is the source of carbon of the glucose synthesis. Addition of N6, O2′‐dibutyryl cyclic adenosine 3′:5′‐monophosphate in concentrations of 100 and 10 μM to the perfusion medium resulted in a response similar to that of glucagon. It is suggested that cyclic adenosine 3′:5′‐monophosphate is the mediator of glucagon action in liver. Preperfusion of the isolated livers with insulin diminished the glucagon effects. The glucagon‐stimulation of glucose and urea production was completely suppressed, while the increased ketogenesis was inhibited by 60% in the presence of insulin. Since all three glucagon responses were inhibited, this supports the concept that insulin lowers, in some way, the elevation of cyclic adenosine 3′:5′‐phosphate which occurs following glucagon administration. That insulin does not exert its effect subsequent to cyclic adenosine 3′:5′‐phosphate is suggested by the observation that insulin, under the same conditions which inhibited the response of liver to glucagon, had little or no effect on the increases in gluconeogenesis, ureogenesis, and ketogenesis following, dibutyryl cyclic adenosine‐3′:5′‐phosphate. Since an effect of insulin on cyclic adenosine 3′:5′‐phosphate phosphodiesterase seems unlikely, it is suggested that the inhibition of glucagon responses by insulin is the result of an interaction at the adenyl cyclase or one of the step(s) between binding of the hormone and the enzyme.

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Liver 3': 5'-Nucleotide Phosphodiesterase and its Activity in Rat Livers Perfused with Insulin

Cited by 72 publications

References 27 publications

Hormone Action on Liver Adenyl Cyclase Activity

Hormone Action on Liver Adenyl Cyclase Activity

Heat treatment induces an increase in intracellular cyclic AMP content in human epidermoid A-431 cells

Interactions of Glucagon and Insulin on the Metabolism of Perfused Livers from Fasted Rats

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