The metabolism of exogenous cyclic AMP at low concentrations by thymic lymphocytes

MacManus, J. P.; Whitfield, J. F.; Braceland, B M

doi:10.1016/0006-291x(71)90399-8

Cited by 56 publications

(6 citation statements)

References 8 publications

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“…This makes it possible to speculate that the two dimorphs of phosphodiesterase could provide adequate means of controlling phosphodies- (156)(157)(158). In tissues from a variety of hypertensive rats, the intracellular levels of cyclic nucleotides are inversely correlated with the Form I1 activity present (141-143 The significance of the presence of two main enzymes with two widely varying affinities for the hydrolysis of either cyclic nucleotide is not entirely clear.…”

Section: General Considerationsmentioning

confidence: 99%

Cyclic Nucleotide Phosphodiesterases: Properties, Activators, Inhibitors, Structure–Activity Relationships, and Possible Role in Drug Development

Amer

Kreighbaum

1975

Journal of Pharmaceutical Sciences

205

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Section: General Considerationsmentioning

confidence: 99%

Cyclic Nucleotide Phosphodiesterases: Properties, Activators, Inhibitors, Structure–Activity Relationships, and Possible Role in Drug Development

Amer

Kreighbaum

1975

Journal of Pharmaceutical Sciences

205

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“…The points are the means ± SEM of eight separate determinations. PGE I action (MacManus and Whitfield 1969) without ente ring the cell (MacManus, Whitfield and Braceland 1971), or alte ring the intracellular cyclic AMP content (MacManus, unpublished observation), the cyclic AMP produced in the membrane of the PGEI-treated cell probably reacts with a membranebound 'activation site' to produce compounds which migrate to the appropriate intracellular regions where they start the calcium-"Sensitive mitogenic process (Whitfield and MacManus 1972).…”

Section: Discussionmentioning

confidence: 94%

Inhibition by Calcium of the Cyclic AMP-Mediated Stimulation of Thymic Lymphoblast Proliferation by Prostaglandin E₁

Jf¹,

Jp²,

Braceland³

et al. 2009

Horm Metab Res

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During the fust 10 min after exposure of rat thymic Iymphocytes (thymocytes) to a high concentration (5.0 /.I8/m!) of prostagiandin EI (PGE I ) in medium without added calcium, there is a 67-fold rise in the ceUular cyclic AMP content which causes strong stimulations of deoxyribunucleic acid (DNA) synthesis and cell proliferation. On the other hand, in the presence of 1.0 mM calcium, PGE I causes a similar (68-fold) rise in the cellular cyclic AMP content and a strong stimulation of DNA synthesis, but the stimulated cells do not enter mitosis. Thus, calcium selectively inhibits the cyclic AMP-induced mitogenic process.The calcium-sensitive phase of the mitogenic reaction is normally completed by only 2.5 min after exposure to PGE I; addition of calcium to the extracellular fluid at, or after, this time does not inhibit the flow of stimulated cells into mitosis which begins between 3 and 4 hr later. Finally, calcium must inhibit the operation, but not the cyclic AMPmediated activation, of the mitogenic system since the inhibition can be fully relieved by removal of calcium at least 4 br after exposure to PGE I.

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“…In most tissues the low Km form has been localized in particulate or membrane fractions. The subcellular distribution of the low Km form is largely unknown, but extracellularly active membrane-bound PDE may be a general phenomenon since degradation of extracellular cAMP has previously been reported for other tissues(MacManus et al 1971; Szabo 8c Burke 1972;Chassy 1972; Woo 8c Manery 1973).The advantage of measuring extracellular PDE activity is that the enzyme is studied in situ. Hormonal stimulation of extracellular PDE in intact tissues…”

mentioning

confidence: 95%

Stimulatory Effect of FSH in Vitro on the Extracellularly Active Cyclic Amp Phosphodiesterase in the Prepubertal Rat Ovary

Selstam

Rosberg

1976

Acta Endocrinologica

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Intact prepubertal rat ovaries were incubated with radioactively labelled adenosine 3,\m=' \5\m=' \-cyclicmonophosphate (cAMP) in Krebs bicarbonate buffer containing glucose. The rate of degradation of cAMP was determined by measuring the radioactivity in the medium after precipitation with Ba(OH)2 and ZnSO4. The fate of the nucleotide was followed by measuring the products in the incubation medium. Paper chromatography was used for the separation and identification of these products. It was found that cAMP was degraded to AMP, which in turn was degraded to inorganic phosphate (Pi) and adenosine. An uptake of labelled products was also observed. NIH-FSH-S9 (10 and 100 \g=m\g/ml), but not NIH-LH-B8 (0.1\p=n-\100\g=m\g/ml),increased the degradation of cAMP. Concomitantly, an increased accumulation of labelled adenosine and Pi as well as an increased uptake of labelled products were seen. Kinetic studies with low concentrations of cAMP (0.125\p=n-\0.025\g=m\mol/l) revealed an apparent Km value of 0.12 \g=m\mol/lfor the phosphodiesterase (PDE) activity. FSH significantly changed the slope of the curve in the Lineweaver-Burk plot by increasing the PDE activity. The increased PDE activity in the presence of FSH is discussed in relation to earlier findings of differences in action between LH and FSH on the cAMP system in the prepubertal rat ovary.A stimulatory effect of LH on the ovarian cAMP system is well documented, while an effect of FSH has been shown for a few species only. In the pre¬ pubertal rat ovary both LH and FSH increase adenylate cyclase activity

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The metabolism of exogenous cyclic AMP at low concentrations by thymic lymphocytes

Cited by 56 publications

References 8 publications

Cyclic Nucleotide Phosphodiesterases: Properties, Activators, Inhibitors, Structure–Activity Relationships, and Possible Role in Drug Development

Cyclic Nucleotide Phosphodiesterases: Properties, Activators, Inhibitors, Structure–Activity Relationships, and Possible Role in Drug Development

Inhibition by Calcium of the Cyclic AMP-Mediated Stimulation of Thymic Lymphoblast Proliferation by Prostaglandin E₁

Stimulatory Effect of FSH in Vitro on the Extracellularly Active Cyclic Amp Phosphodiesterase in the Prepubertal Rat Ovary

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The metabolism of exogenous cyclic AMP at low concentrations by thymic lymphocytes

Cited by 56 publications

References 8 publications

Cyclic Nucleotide Phosphodiesterases: Properties, Activators, Inhibitors, Structure–Activity Relationships, and Possible Role in Drug Development

Cyclic Nucleotide Phosphodiesterases: Properties, Activators, Inhibitors, Structure–Activity Relationships, and Possible Role in Drug Development

Inhibition by Calcium of the Cyclic AMP-Mediated Stimulation of Thymic Lymphoblast Proliferation by Prostaglandin E1

Stimulatory Effect of FSH in Vitro on the Extracellularly Active Cyclic Amp Phosphodiesterase in the Prepubertal Rat Ovary

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Inhibition by Calcium of the Cyclic AMP-Mediated Stimulation of Thymic Lymphoblast Proliferation by Prostaglandin E₁