scholarly journals Increased intracellular cyclic adenosine monophosphate inhibits T lymphocyte-mediated cytolysis by two distinct mechanisms.

1988 ◽  
Vol 167 (6) ◽  
pp. 1963-1968 ◽  
Author(s):  
L S Gray ◽  
J Gnarra ◽  
E L Hewlett ◽  
V H Engelhard
Keyword(s):  
Cholera Toxin ◽  
T Lymphocyte ◽  
Pertussis Toxin ◽  
Target Cell ◽  
Cyclic Adenosine Monophosphate ◽  
Second Messenger ◽  
Adenosine Monophosphate ◽  
Dose Dependent Fashion ◽  
Dose Dependent ◽  
Stimulation Of

Cholera toxin (CT), but not pertussis toxin (PT), treatment of cloned murine CTL inhibited target cell lysis in a dose-dependent fashion. The effects of CT were mimicked by forskolin and cyclic adenosine monophosphate (cAMP) analogues. Inhibition of cytotoxicity by CT and cAMP analogs was mediated in part by attenuation of conjugate formation. Additionally, both CT and cAMP analogs blocked the increase in intracellular Ca2+ induced by stimulation of the TCR complex by mAbs. These findings indicate that cAMP inhibits the activity of CTL by two distinct mechanisms and suggests a role for this second messenger in CTL-mediated cytolysis.

Polydatin Attenuates Carbachol-induced Contraction of Guinea Pig Gallbladder

2019 ◽  
Vol 18 (1) ◽  
pp. 34-38
Author(s):  
Chen Lei ◽  
Pan Xiang ◽  
Shen Yonggang ◽  
Song Kai ◽  
Zhong Xingguo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Guinea Pig ◽  
Smooth Muscles ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Dependent Manner ◽  
Underlying Mechanisms ◽  
Dose Dependent

The aim of this study was to determine whether polydatin, a glucoside of resveratrol isolated from the root of Polygonum cuspidatum, warranted development as a potential therapeutic for ameliorating the pain originating from gallbladder spasm disorders and the underlying mechanisms. Guinea pig gallbladder smooth muscles were treated with polydatin and specific inhibitors to explore the mechanisms underpinning polydatin-induced relaxation of carbachol-precontracted guinea pig gallbladder. Our results shown that polydatin relaxed carbachol-induced contraction in a dose-dependent manner through the nitric oxide/cyclic guanosine monophosphate/protein kinase G and the cyclic adenosine monophosphate/protein kinase A signaling pathways as well as the myosin light chain kinase and potassium channels. Our findings suggested that there was value in further exploring the potential therapeutic use of polydatin in gallbladder spasm disorders.

Abstract 003: Progenitor Cells Suppress T-Lymphocyte Proliferation Via a Paracrine Mechanism

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Frederieke van den Akker ◽  
Krijn R Vrijsen ◽  
Janine C Deddens ◽  
Pieter A Doevendans ◽  
Joost P Sluijter
Keyword(s):  
Stem Cell ◽  
T Lymphocytes ◽  
Cell Therapy ◽  
T Lymphocyte ◽  
Stem Cell Therapy ◽  
Lymphocyte Proliferation ◽  
Paracrine Factors ◽  
T Lymphocyte Proliferation ◽  
Dose Dependent Fashion ◽  
Dose Dependent

PURPOSE: Limited treatment options are available for heart failure patients. Stem cell therapy has recently become a potential new way of repairing injured cardiac tissue. Different progenitor cell sources have been investigated, but most promising for cardiac therapy are mesenchymal stem cells (MSC) and cardiomyocyte progenitor cells (CMPC). Cardiac stem cell therapy using MSC or CMPC improved cardiac function, despite low engraftment of the cells. Paracrine factors, produced by the injected cells, presumably cause these improvements. Many studies are performed on the paracrine effects, yet modulation of the immune response in cardiac stem cell therapy, especially the strong influence of T-lymphocytes on adverse remodeling, has not been explored extensively. Methods: Human fetal MSC and CMPC were characterized and tested for multipotency. The immunosuppressive properties of both cell types were tested in co-culture with allogeneic peripheral blood mononuclear cells (PBMC) or T-lymphocytes stimulated with IL-2 and PMA. Proliferation was measured by CFSE-analysis using flow cytometry. Results: Proliferation of PBMC and T-lymphocytes was significantly reduced in the presence of MSC (65 ± 8%) or CMPC (97 ± 0.6%). In addition, production of inflammatory cytokines IFN-gamma and TNF-alpha was strongly downregulated. This effect was observed in both direct cell contact as well as in transwell co-culture systems (MSC: 58 ± 10%; CMPC: 62 ± 9%). Transfer of conditioned medium from these co-cultures to unrelated, activated PBMC or T-lymphocytes abrogated proliferation in these cells to a similar extent as the original co-culture (MSC: 51 ± 8%; CMPC: 97 ± 0.7%). Interestingly, exosomes isolated from the conditioned medium of MSC and CMPC prevented T-lymphocyte proliferation in a dose-dependent fashion. At a concentration of 1.5μg, T-lymphocyte proliferation was significantly suppressed (MSC-exosomes: 73 ± 12%; CMPC-exosomes: 77 ± 10%). Conclusion: Both MSC and CMPC have a strong capacity for in vitro immunosuppression, which is mediated by paracrine factors. One potent immunosuppressive factor secreted by both MSC and CMPC are exosomes, which prevented T-lymphocyte proliferation in a dose-dependent fashion.

Interaction of adenosine with vasopressin in the inner medullary collecting duct

1990 ◽  
Vol 259 (4) ◽  
pp. F679-F687 ◽  
Author(s):  
Y. Yagil
Keyword(s):  
Pertussis Toxin ◽  
Receptor Agonist ◽  
Collecting Duct ◽  
Phosphodiesterase Inhibitor ◽  
Inhibitory Effects ◽  
Inner Medullary Collecting Duct ◽  
Medullary Collecting Duct ◽  
Camp Levels ◽  
Dose Dependent ◽  
Stimulation Of

Administration of adenosine (Ado) into rat renal artery induces dose-dependent diuresis that is independent of changes in glomerular filtration rate or renal blood flow, suggesting a direct effect on tubule H2O reabsorption. To test the hypothesis that Ado modulates cellular action of arginine vasopressin (AVP) as a tubular mechanism for the diuretic effect of Ado, interaction of Ado with AVP was studied in primary cell culture of rat inner medullary collecting duct (IMCD) epithelium. Stimulation of cells with 10(-6) M AVP in presence of 0.1 mM Ro 20-1724, a nonmethylxanthine phosphodiesterase inhibitor that has no effect on Ado receptors, increased adenosine 3',5'-cyclic monophosphate (cAMP) levels twofold or more above baseline. Stimulation of cells with the A1 Ado-receptor agonist N6-cyclohexyladenosine (CHA), the A2-receptor agonist 5'-(N-ethylcarboxamido)-adenosine (NECA), or with the P-site agonist 2',5'-dideoxyadenosine (DDA) significantly inhibited the AVP-stimulated cAMP response. Preincubation with pertussis toxin abolished the inhibitory effects of CHA and NECA, but not of DDA. The data suggest that, in the rat IMCD, Ado modulates AVP action by interfering with its ability to stimulate formation of its second messenger, cAMP. This effect is mediated by the extracellular Ado receptors A1 and A2 and by the intracellular P-site. It occurs by at least two pathways, one sensitive and the other insensitive to pertussis toxin.

scholarly journals Interleukin-4 gene expression in activated human T lymphocytes is regulated by the cyclic adenosine monophosphate-dependent signaling pathway

Blood ◽  
1996 ◽  
Vol 87 (2) ◽  
pp. 691-698 ◽  
Author(s):  
P Borger ◽  
HF Kauffman ◽  
DS Postma ◽  
E Vellenga
Keyword(s):  
T Lymphocytes ◽  
Signaling Pathway ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Interleukin 4 ◽  
Con A ◽  
Activated T Cells ◽  
Gm Csf ◽  
Dose Dependent ◽  
Dependent Signaling Pathway

In the present study, we have investigated the involvement of the cyclic adenosine monophosphate (cAMP)-dependent signaling pathway on interleukin-4 (IL-4) gene expression in freshly isolated human T lymphocytes. 2′–0-dibutyryl cAMP (db-cAMP) and prostaglandin E2 (PGE2) were used to directly and indirectly activate the protein kinase A pathway. Northern analysis showed that concanavalin A (Con A)-, anti- CD3 (alpha CD3)-, or anti-CD3 plus anti-CD28 (alpha CD3/alpha CD28)- induced accumulation of IL-4 mRNA was inhibited by db-cAMP (10(-3) mol/L). Db-cAMP showed a steep dose-dependent inhibition; concentrations or = 10(-4) mol/L did not affect IL-4 mRNA accumulation. In contrast, GM-CSF mRNA expression showed a wider dose- dependent range; 10(-5) mol/L db-cAMP still affected GM-CSF accumulation. PGE2 inhibited the Con A- and alpha CD3/alpha CD28- induced accumulation of IL-4 mRNA in a dose-dependent fashion. Con A- induced IL-4 mRNA was inhibited by 10(-4) to 10(-7) mol/L PGE2; alpha CD3/alpha CD28-induced IL-4 mRNA was inhibited by 10(-5) to 10(-8) mol/L PGE2. Nuclear run-on experiments showed that the inhibitory effects of db-cAMP and PGE2 were accomplished at transcriptional level in Con A-activated T cells, whereas changes at transcriptional and posttranscriptional level were involved in alpha CD3/alpha CD28- activated T lymphocytes. In contrast to Con A and alpha CD3/alpha CD28 activation, phorbol myristate acetate plus A23187-induced IL-4 mRNA expression was insensitive to the inhibitory effect of db-cAMP and PGE2. Moreover, it appeared that the sensitivity for cAMP-mediated downregulation could not be blocked by stimulation T lymphocytes with alpha CD3/alpha CD28 in the presence of IL-2, IL-7, IL-10, IL-12, or a combination of these cytokines. Finally, it was shown that, in accordance with the mRNA studies, db-cAMP and PGE2 suppressed the IL-4 secretion in Con A- and alpha CD3/alpha CD28-activated T cells. In conclusion, these data show that IL-4 expression is negatively regulated by the protein kinase A-dependent signaling pathway by transcriptional and posttranscriptional mechanisms that depend on costimulatory signals.

Secondary Messenger Systems in PTSD

2016 ◽  
Author(s):  
Ulrike Schmidt
Keyword(s):  
Second Messengers ◽  
Cyclic Adenosine Monophosphate ◽  
Second Messenger ◽  
Adenosine Monophosphate ◽  
Cyclic Guanosine Monophosphate ◽  
Brain Regions ◽  
Guanosine Monophosphate ◽  
Intracellular Camp ◽  
Post Traumatic Stress ◽  
Secondary Messenger

Second messengers such as cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), inositoltriphosphate, and diacylglycerol (DAG) are a prerequisite for the signal transduction of extracellular receptors. The latter are central for cellular function and thus are implicated in the pathobiology of a variety of disorders, such as schizophrenia, bipolar disorder, major depression, and post-traumatic stress disorder (PTSD). This chapter focuses on the involvement of second messenger molecules and their regulators as direct targets in human and animal PTSD and aims to stimulate the underdeveloped research in this field. The synthesis of literature reveals that second messengers clearly play a central role in PTSD-associated brain regions and processes. In particular, pituitary adenylate cyclase-activating polypeptide (PACAP), an important regulator of intracellular cAMP levels, as well as protein kinase c, the major target of DAG, belong to the hitherto most promising PTSD candidate molecules directly involved in second messenger signaling.

Effects of cholera toxin and isobutylmethylxanthine on growth of human fibroblasts

1986 ◽  
Vol 251 (2) ◽  
pp. C238-C246 ◽  
Author(s):  
B. Espinoza ◽  
W. Wharton
Keyword(s):  
Cholera Toxin ◽  
Human Fibroblasts ◽  
Phosphodiesterase Inhibitor ◽  
Serum Starvation ◽  
Final Density ◽  
Low Concentrations ◽  
High Concentrations ◽  
Dose Dependent Decrease ◽  
Dose Dependent ◽  
Stimulation Of

Cholera toxin produced a dose-dependent decrease in the restimulation of G0/G1 traverse in density-arrested human fibroblasts but did not inhibit the stimulation of cells arrested in G0 after serum starvation at low density. In addition, cholera toxin did not inhibit the proliferation of sparse logarithmically growing human fibroblasts, even when low concentrations of the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) were also present. However, the final density to which sparse cells grew was limited by cholera toxin, when added either alone or together with low concentrations of IBMX. In contrast, high concentrations of the phosphodiesterase inhibitor alone produced a profound inhibition in the growth of sparse human fibroblasts. IBMX produced an inhibition both in the G1 and in the G2 phases of the cell cycle by a mechanism(s) that was not related to the magnitude of the increases in adenosine 3',5'-cyclic monophosphate concentrations.

Noradrenergic Stimulation of Cyclic Adenosine Monophosphate in Rat Purkinje Neurons: An Immunocytochemical Study

Science ◽  
1973 ◽  
Vol 179 (4073) ◽  
pp. 585-588 ◽  
Author(s):  
G. R. Siggins ◽  
E. F. Battenberg ◽  
B. J. Hoffer ◽  
F. E. Bloom ◽  
A. L. Steiner
Keyword(s):  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Purkinje Neurons ◽  
Immunocytochemical Study ◽  
Stimulation Of
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