THE PROPERTIES OF AN ADENINE RIBONUCLEOTIDE PRODUCED WITH CELLULAR PARTICLES, ATP, Mg<sup>++</sup>, AND EPINEPHRINE OR GLUCAGON

Sutherland, Earl W.; Rall, T. W.

doi:10.1021/ja01570a087

Cited by 212 publications

(53 citation statements)

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“…It is significant that whereas lung tissue is richly endowed with ,-adrenergic receptors, it lacks receptors to most of the other agonists which did not stimulate tumour growth in the lungs. An allosteric interaction between an agonist and its corresponding receptor, bound to adenyl cyclase (AC) usually causes an increase in the concentration of the intracellular "second messenger", adenosine-3' -5'-monophosphate cyclic (c-AMP), which is synthesized when AC is activated in the presence of complement (Sutherland and Rall, 1957;Robinson et al, 1971). Cyclic AMP is cleaved to AMP-5' by intracellular phosphodiesterase (PD); consequently, theophylline and its derivatives which inhibit PD increase the effects of ,8-agonists on tissue c-AMP.…”

Section: -Hydroxytryptamine (50h-t)mentioning

confidence: 99%

Lowering of innate resistance of the lungs to the growth of blood-borne cancer cells in states of topical and systemic stress

Brenk¹,

Stone²,

Kelly³

et al. 1976

Br J Cancer

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Section: -Hydroxytryptamine (50h-t)mentioning

confidence: 99%

Lowering of innate resistance of the lungs to the growth of blood-borne cancer cells in states of topical and systemic stress

Brenk¹,

Stone²,

Kelly³

et al. 1976

Br J Cancer

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“…ince its discovery by Sutherland and Rall in the 1950s, 1 cAMP has been recognized for its essential role in cellular functions that include proliferation, control of cell shape, excitability, gene expression, metabolism, differentiation, apoptosis, and ion homeostasis. However, nowhere have the functional consequences of cAMP been better defined than in control of the endothelial barrier.…”

mentioning

confidence: 99%

Paradoxical cAMP-Induced Lung Endothelial Hyperpermeability Revealed by Pseudomonas aeruginosa ExoY

Sayner

Frank

King

et al. 2004

Circulation Research

111

166

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Abstract-Mammalian transmembrane adenylyl cyclases synthesize a restricted plasmalemmal cAMP pool that is intensely endothelial barrier protective. Bacteria have devised mechanisms of transferring eukaryotic factor-dependent adenylyl cyclases into mammalian cells. Pseudomonas aeruginosa ExoY is one such enzyme that catalyzes cytosolic cAMP synthesis, with unknown function. Pseudomonas aeruginosa genetically modified to introduce only the ExoY toxin elevated cAMP 800-fold in pulmonary microvascular endothelial cells over 4 hours, whereas a catalytically deficient (ExoY K81M ) strain did not increase cAMP. ExoY-derived cAMP was localized to a cytosolic microdomain not regulated by phosphodiesterase activity. In contrast to the barrier-enhancing actions of plasmalemmal cAMP, the ExoY cytosolic cAMP pool induced endothelial gap formation and increased the filtration coefficient in the isolated perfused lung. These findings collectively illustrate a previously unrecognized mechanism of hyperpermeability induced by rises in cytosolic cAMP.

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“…With the discovery that cAMP acts as a second "messenger" in regulating hormone-dependent cellular processes, such as differentiation, proliferation, and function (1,2), attention inevitably turned to the possible role of cAMP in antigendependent cellular events. There is now much evidence that cAMP is a protagonist in the activation and functioning of immunocytes responding to antigen (3,4).…”

mentioning

confidence: 99%

Cyclic AMP and immune responses: changes in the splenic level of cyclic AMP during the response of mice to antigen.

Plescia¹,

Yamamoto²,

Shimamura³

1975

Proc. Natl. Acad. Sci. U.S.A.

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Intravenous injection of sheep erythrocytes into normal immunologically competent C57BI/6J mice results in significant and characteristic changes in the splenic level of 3':5'-cAMP with initiation of the immune response and proliferation of antibody-forming cells. The level increases 2-to 3-fold initially, peaks at 2 min, and returns to base level in an hour. Between 2 and 5 days there is a decrease, followed by a peak when the rate of proliferation of antibody-forming cells is maximal. Changes in splenic level of cAMP are thus transitory and biphasic, and they occur only in response to foreign substances that are immunogenic, such as heterologous erythrocytes, and not to antigenically inert carbon particles. They are also dependent upon the dose of immunogen. Moreover, the double-stranded hybrid of polyadenylate and polyuridylate, which acts synergistically with antigen in stimulating endogenous cAMP, is immunoenhancing if given with sheep erythrocytes when the cAMP level is increasing, and immunosuppressive if given when cAMP is decreasing. These data provide direct evidence for a role of cAMP as a mediator in the activation and proliferation of immunocytes stimulated by antigen. With knowledge of the transitory and biphasic nature of the cAMP response induced by antigen, one can avoid indiscriminate use of drugs that modify the level of endogenous cAMP and instead employ them rationally in controlling the immune response, enhancing or suppressing it as desired.With the discovery that cAMP acts as a second "messenger" in regulating hormone-dependent cellular processes, such as differentiation, proliferation, and function (1, 2), attention inevitably turned to the possible role of cAMP in antigendependent cellular events. There is now much evidence that cAMP is a protagonist in the activation and functioning of immunocytes responding to antigen (3, 4). The evidence with respect to activation is largely indirect and is based on the effect of stimulators of biosynthesis of endogenous cAMP on the immune response to antigens. One interpretation of this effect is that antigen itself, on reacting with immunocytes,

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THE PROPERTIES OF AN ADENINE RIBONUCLEOTIDE PRODUCED WITH CELLULAR PARTICLES, ATP, Mg⁺⁺, AND EPINEPHRINE OR GLUCAGON

Cited by 212 publications

References 1 publication

Lowering of innate resistance of the lungs to the growth of blood-borne cancer cells in states of topical and systemic stress

Lowering of innate resistance of the lungs to the growth of blood-borne cancer cells in states of topical and systemic stress

Paradoxical cAMP-Induced Lung Endothelial Hyperpermeability Revealed by Pseudomonas aeruginosa ExoY

Cyclic AMP and immune responses: changes in the splenic level of cyclic AMP during the response of mice to antigen.

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THE PROPERTIES OF AN ADENINE RIBONUCLEOTIDE PRODUCED WITH CELLULAR PARTICLES, ATP, Mg++, AND EPINEPHRINE OR GLUCAGON

Cited by 212 publications

References 1 publication

Lowering of innate resistance of the lungs to the growth of blood-borne cancer cells in states of topical and systemic stress

Lowering of innate resistance of the lungs to the growth of blood-borne cancer cells in states of topical and systemic stress

Paradoxical cAMP-Induced Lung Endothelial Hyperpermeability Revealed by Pseudomonas aeruginosa ExoY

Cyclic AMP and immune responses: changes in the splenic level of cyclic AMP during the response of mice to antigen.

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THE PROPERTIES OF AN ADENINE RIBONUCLEOTIDE PRODUCED WITH CELLULAR PARTICLES, ATP, Mg⁺⁺, AND EPINEPHRINE OR GLUCAGON