The Effects of Epinephrine and Prostaglandin E1 on Cyclic Adenosine 3′ : 5′-Monophosphate Levels in WI-38 Fibroblasts

Kelly, Lewis; Butcher, R.W.

doi:10.1016/s0021-9258(19)42643-4

Cited by 86 publications

(3 citation statements)

References 23 publications

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“…The extrusion of intracellular cyclic AMP into the surrounding medium, first demonstrated in pigeon erthrocytes (5), has now been widely observed (2,4,10,12,13,18,19), but in most cases neither the mechanism of extrusion nor the biological significance of the process is understood . The only clear insight into the physiological role of extracellular cyclic AMP comes from work with certain cellular slime molds, such as Dictyostelium discoideum, in which external cyclic AMP behaves as a primary messenger for cellular morphogenesis and also serves as a powerful chemoattractant (8).…”

Section: Discussionmentioning

confidence: 99%

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Evidence for a pronounced secretion of cyclic AMP by Tetrahymena.

Nandini-Kishore¹,

Thompson²

1980

The Journal of Cell Biology

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The unicellular eukaryote Tetrahymena pyriformis secretes significant amounts of cyclic AMP into its external medium . Cells transferred from growth medium into any of the following three different non-nutrient media: (a) 5 mM phosphate buffer containing 47 mM NaCl and 1 MM MgS0 4 , (b) 10 mM Tris, or (c) 1 .3 mM Tris containing I mM citrate and 1 mM Ca(OH)2, released to the outside almost 60-80% of the total cyclic AMP produced during 2-5 h of incubation . Tris-citrateCa+2 medium was chosen for further experiments because of its minimal nonspecific interference in the cyclic AMP radioimmunoassay.The identity of the secreted material recognized as cyclic AMP by radioimmunoassay was confirmed by demonstrating its almost complete hydrolysis with commercial beef heart phosphodiesterase . Furthermore, the radioimmunoassayactive material in the concentrated medium co-chromatographed on paper with [3H]cyclic AMP, as judged by assay of the eluted material.After resuspending cells in Tris-citrate-Ca 2+ medium, the extracellular concentration of cyclic AMP rose steadily over a 5-h period, reaching a level equivalent to -35-50 pmol cyclic AMP/ 106 cells vs . an internal cyclic AMP quantity at 5 h of 8-10 pmol/106 cells . After 5 h, the level of extracellular cyclic AMP reached a plateau . There was no degradation or uptake of external cyclic AMP by the cells during this period .The unicellular eukaryote Tetrahymena pyriformis has been shown to vary its intracellular concentration of cyclic AMP under different physiological conditions (6, 27) . Tetrahymena has also been reported to contain an adenylate cyclase that responds in vitro to,ß-adrenergic agonists. Our own recent analyses (15) produced evidence suggesting that agents that depolarize the plasma membrane can raise internal cyclic AMP levels. In the course of this work, we also discovered that Tetrahymena secretes cyclic AMP into its medium. Because the secretion of cyclic AMP has been detected in several cell types (2,4,8,10,12,13,18,19) and is known to serve a regulatory function in some cases (8, 14), we initiated the present study to characterize the extrusion of cyclic AMP by Tetrahymena. MATERIALS AND METHODS Culture Conditions for Normal GrowthUnless specified otherwise, T pyriformis NT-I wasgrown with shaking in medium containing 2% proteose peptone, 0.290 yeast extract, 0.5`7 glucose, and a trace of chelated iron (23) at 28°C and allowed to reach the mid-logarithmic phase of growth (1 x 10°to 2 x 10'' cells/ml). Starvation ConditionsA measured volume (100-1,000 ml) of the above cell suspension (depending on the number of cells required for a given experiment) was centrifuged at 800 g at 4°C in a Sorvall RC-2B refrigerated centrifuge (DuPont Instruments-Sorvall, DuPont Co., Newtown, Conn .) for 5 min. After immediate aspiration of the supernate, the cells were pooled and washed in 200 ml of inorganic medium consisting of 47 mM NaCl and I MM MgS0 . , in 5 mM potassium phosphate buffer, pH 7.2 (9). J. CELL BIOLOGY

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Section: Discussionmentioning

confidence: 99%

“…In the course of this work, we also discovered that Tetrahymena secretes cyclic AMP into its medium. Because the secretion of cyclic AMP has been detected in several cell types (2,4,8,10,12,13,18,19) and is known to serve a regulatory function in some cases (8,14), we initiated the present study to characterize the extrusion of cyclic AMP by Tetrahymena.…”

mentioning

confidence: 99%

Evidence for a pronounced secretion of cyclic AMP by Tetrahymena.

Nandini-Kishore¹,

Thompson²

1980

The Journal of Cell Biology

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“…Further studies revealed that various mammalian cells such as adipocytes, hepatocytes, and certain neuronal cells can release cAMP into the extracellular environment. [ 57–66 ] The release of cAMP into the extracellular environment is energy dependent. [ 49–52,66 ] However, the biological activity and mechanism of action of extracellular cAMP remained elusive.…”

Section: Camp Signaling Cascade In Mammalian Cell Physiology: Historical Role Of Extracellular Campmentioning

confidence: 99%

Extracellular cAMP: The Past and Visiting the Future in cAMP‐Enriched Extracellular Vesicles

et al. 2021

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It is recently discovered that the cyclic nucleotide, cyclic adenosine monophosphate (cAMP) can be enriched in the extracellular vesicles (EVs) isolated from endothelial cells. In the current perspective a historical context for the discovery of the extracellular cAMP is provided. The story of extracellular cAMP through investigations addressing the molecule's role in the adenosine pathway is followed, which is widespread in mammalian physiology. The adenosine pathway mediates normal physiological conditions such as renin release, phosphate transport, etc., and participates in pathological conditions such as bronchoconstriction of the airways. Furthermore, adenosine mediated biological pathways are regulated via the receptor mediated intracellular cAMP pathway in mammalian cells. It then speculates on the question of whether cAMP enriched EVs could bypass typical receptor mediated cell signaling and directly activate cAMP signaling cascade in target cells. Preliminary studies to suggest cAMP enriched EVs are provided, added to naïve endothelial cells, results in an increase in intracellular cAMP. An alternate mechanism is proposed, apart from the traditional adenosine pathway, that extracellular cAMP may exert its effects and put into perspective how it might consider circulating cAMP moving forward.

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