Evaluation of the Liver Adenosine 3′,5′-Monophosphate Response to Glucagon

Pauk, George L.; Reddy, William J.

doi:10.2337/diab.20.3.129

Cited by 22 publications

(8 citation statements)

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“…The time course of cyclic AMP after glucagon as shown in Fig.2 is at variance with some of the data reported in the literature indicating a more rapid return to basal levels [34,35]. This, however, may be the consequence of significant stress applied to the animals concomitant with the glucagon injection.…”

Section: Kinetics Of Total Cyclic Amp Protein-bound Cyclic Ampand Prsupporting

confidence: 80%

Protein‐Bound Adenosine 3′:5′‐Monophosphate in Liver of Glucagon‐Treated Rats

Schwoch

Hilz

1977

European Journal of Biochemistry

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The adenosine 3' : 5'-monophosphate (cyclic AMP) fraction bound to high-affinity proteins of rat liver cytosol was determined by homogenization of the frozen tissue with a charcoal suspension followed by centrifugation. Protein-bound cyclic AMP in the supernatant appears to represent mainly or exclusively cyclic AMP bound to the regulatory subunit of protein kinases as indicated by its identity with the phosphodiesterase-resistant cyclic AMP fraction in homogenates and its close correlation with protein kinase activation in vivo.Parallel determination of total cyclic AMP, protein-bound cyclic AMP and protein kinase activation in the livers of rats sacrificed between 2 and 120 min after glucagon injection made it possible to correlate these parameters at different levels of total cyclic AMP in vivo. In non-stimulated tissue, total cyclic AMP was 0.7 pmol/mg tissue, about 50 % being present in the form of protein-bound cyclic AMP. At a total cyclic AMP level of 1.1 -1.2 pmol/mg, half-maximal values for bound cyclic AMP as well as half-maximal activation of protein kinases were found. This shows not only a close correlation between these two parameters but also indicates that rather small changes in total cyclic AMP are required in vivo to effect binding of cyclic AMP to the regulatory subunit, R, with the concomitant activation of protein kinase.The reliability of protein-bound cyclic AMP as an indicator of protein kinase activation was further documented in the livers of stressed animals, in which total cyclic AMP was elevated nearly two-fold while bound cyclic AMP and protein kinase remained at basal values.

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Section: Kinetics Of Total Cyclic Amp Protein-bound Cyclic Ampand Prsupporting

confidence: 80%

Protein‐Bound Adenosine 3′:5′‐Monophosphate in Liver of Glucagon‐Treated Rats

Schwoch

Hilz

1977

European Journal of Biochemistry

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“…The high activity of protein kinase I at relatively low intracellular cyclic AMP concentrations suggests that physiological conditions that only slightly increase the cyclic AMP concentration, for instance starvation (Pauk & Reddy, 1971), primarily activate the protein kinase type I. This would be in accordance with determinations of the dissociation constants of isolated liver protein kinases, indicating a lower affinity for cyclic AMP for protein kinase IL and a higher one for protein kinase I (Yamamura et al, 1971;Kumon et al, 1972;Granner, 1974).…”

Section: Discussionmentioning

confidence: 69%

Differential activation of type-I and type-II adenosine 3′:5′-cyclic monophosphate-dependent protein kinases in liver of glucagon-treated rats

Schwoch¹

1978

Biochemical Journal

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The protein-bound cyclic AMP and the activity of cytosolic protein kinases in the presence and absence of cyclic AMP were determined in rat liver up to 2h after injection of glucagon. On the basis of the different salt-sensitivities of the activated cyclic AMP-dependent proteinkinases I and II, an activation of protein kinase II restricted to the high cyclic AMP concentrations present in the first 30 min after hormone injection was found. Essentially the same result was obtained by chromatographic analysis on DEAE-cellulose of liver cytosol from untreated rats and from rats killed at 2 and 60 min after glucagon injection. Protein kinase II activation was only detected at 2 min after injection. In contrast, the cyclic AMP-dependent protein kinase I was found to be nearly totally activated at 2 min and to be still almost as active at 60 min after the hormone stimulus, whereas the amount of bound cyclic AMP and the activation of total cytosolic protein kinases had fallen to two-thirds of their maximal values during this time period. A third cyclic AMP-independent protein kinase, which co-chromatographed with protein kinase type II, could be clearly distinguished from the two cyclic AMP-dependent kinases by use of the heat-stable inhibitor from bovine muscle, which totally inhibited the cyclic AMP-dependent enzymes, but stimulated the cyclic AMP-independent protein kinase.

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“…by treatment of the animals with L-methyl prednisolone (11). Such changes in phosphodiesterase activity could be a cause for the observed decrease in responsiveness of the rat liver to glucagon after adrenalectomy (12) and the effects of hydrocortisone on liver glycogen metabolism (3). The "permissive" effects of corticosteroids in perfused rat liver anid heart have been extensively doctumented by Extoni et al, who, however, have postulated a different imiechaniism of corticosteroid actioni (13,14).…”

Section: Methodsmentioning

confidence: 99%

An Effect of Dexamethasone on Adenosine 3′,5′ -Monophosphate Content and Adenosine 3′,5′ -Monophosphate Phosphodiesterase Activity of Cultured Hepatoma Cells

Manganiello¹,

Vaughan²

1972

J. Clin. Invest.

115

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A B S T R A C T The effect of dexamethasone on adenosine 3',5'-monophosphate (cAMP) phosphodiesterase activity in cultured HTC hepatoma cells was investigated.Homogenates of these cells contain phosphodiesterase activity with two apparent Michaelis constants for cANIP (2-5 uM and 50 uM). At all substrate concentrations tested, phosphodiesterase activity was decreased 25-40% in cells incubated for 36 hr or ;nore with 1 FAM dexamethasone. Acid phosphatase activity in the same cells was not decreased. a-Methyl testosterone, 1 FAM, was without effect on phosphodiesterase activity.Incubation for 10 min with epinephrine plus theophylline increased the cAMP content of the HTC cells 3-to 6-fold. In cells incubated for 72 hr with dexamethasone, the basal concentration of cAMP was slightly increased and the increment produced by epinephrine plus theophylline was markedly increased. We believe that in many cells the so-called permissive effects of steroid hormones on cAMP mediated processes may be due to an effect of these hormones on cAMP phosphodiesterase activity similar to that observed in HTC cells incubated with dexamethasone. INTRODUCTIONIn several tissues, the effects of hormones that presumably elevate the intracellular concentrationi of cyclic adenosine 3',5'-monophosphate (cANIP)1 are enhanced by steroid hormones (1-3). WAe recently observed that Received for publication 25 April 1972 and in revised form 6 July 1972. 1Abbreviations used in this paper: cAMP, cyclic adenosine 3',5'-monophosphate ; dexamethasone,9-fluoro-1l 1%-17,21-trihyd r oxy-16a-methyl-pregma-1,4-diene-3,20-dione,21-phosphate; a-methyl-testosterone, 17-methyl-4-androsten-3-one; PGE1, prostaglandin E1. the cAMP content of HTC hepatoma cells was increased several fold within 10 min after addition of epinephrine (or isoproterenol) and the increment was greater in cells that had been previously incubated with dexamethasone. This effect of dexamethasone and the so-called permissive effects of specific steroid hormones on cAMP mediated processes in other tissues could be secondary to a steroid-induced decrease in cAMP degradation. The homogeneous population of cultured cells appeared to offer an excellent system for investigation of the effects of a steroid hormone on cAMP phosphodiesterase activity. We found, as reported below, that phosphodiesterase activity was markedly decreased by incubation of HTC cells with dexamethasone. These observations are consistent with the view that the permissive effects of certain steroid hormones on processes regulated by cAMP may be the result of steroid-induced diminution in cAMP phosphodiesterase activity. METHODSHTC cells were maintained in monolayer cultures in 250 ml plastic Falcon flasks in Eagle's basal medium (Grand Island Biological Co., Grand Island, N. Y.) supplemented with Earle's salts, 10% fetal calf serum (Grand Island Biological Co.), 2 mm glutamine, 100 U/ml penicillin, and 100 jg/ml streptomycin at 36°C. Cells were detached from the flasks with trypsin, and 4-5 X 105 cells were added to Op...

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Evaluation of the Liver Adenosine 3′,5′-Monophosphate Response to Glucagon

Cited by 22 publications

References 0 publications

Protein‐Bound Adenosine 3′:5′‐Monophosphate in Liver of Glucagon‐Treated Rats

Protein‐Bound Adenosine 3′:5′‐Monophosphate in Liver of Glucagon‐Treated Rats

Differential activation of type-I and type-II adenosine 3′:5′-cyclic monophosphate-dependent protein kinases in liver of glucagon-treated rats

An Effect of Dexamethasone on Adenosine 3′,5′ -Monophosphate Content and Adenosine 3′,5′ -Monophosphate Phosphodiesterase Activity of Cultured Hepatoma Cells

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