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Pharmacology & Therapeutics 2000Despite being known for over 30 years, the functions of the dinucleoside polyphosphates, such as diadenosine 5',5"'-P(1), P(4)-tetraphosphate (Ap(4)A) and diadenosine... (Review)
Review
Despite being known for over 30 years, the functions of the dinucleoside polyphosphates, such as diadenosine 5',5"'-P(1), P(4)-tetraphosphate (Ap(4)A) and diadenosine 5',5"'-P(1), P(3)-triphosphate (Ap(3)A), are still unclear. On the one hand, they may have important signalling functions, both inside and outside the cell (friend), while on the other hand, they may simply be the unavoidable by-products of certain biochemical reactions, which, if allowed to accumulate, would be potentially toxic through their structural similarity to ATP and other essential mononucleotides (foe). Here, the occurrence, synthesis, degradation, and proposed functions of these compounds are briefly reviewed, along with some new data and recent evidence supporting roles for Ap(3)A and Ap(4)A in the cellular decision making processes leading to proliferation, quiescence, differentiation, and apoptosis. Hypotheses are forwarded for the involvement of Ap(4)A in the intra-S phase DNA damage checkpoint and for Ap(3)A and the pFhit (fragile histidine triad gene product) protein in tumour suppression. It is concluded that the roles of friend and foe are not incompatible, but are distinguished by the concentration range of nucleotide achieved under different circumstances.
Topics: Adenosine Triphosphate; Apoptosis; Cell Cycle; Cell Division; DNA Damage; Dinucleoside Phosphates; Humans; Signal Transduction
PubMed: 11007992
DOI: 10.1016/s0163-7258(00)00041-3 -
Advances in Microbial Physiology 1994
Review
Topics: Animals; Bacteria; Dinucleoside Phosphates; Physarum polycephalum; Saccharomyces cerevisiae
PubMed: 7942317
DOI: 10.1016/s0065-2911(08)60177-0 -
British Journal of Pharmacology Aug 2009The purinergic system is composed of mononucleosides, mononucleoside polyphosphates and dinucleoside polyphosphates as agonists, as well as the respective purinergic... (Review)
Review
The purinergic system is composed of mononucleosides, mononucleoside polyphosphates and dinucleoside polyphosphates as agonists, as well as the respective purinergic receptors. Interest in the role of the purinergic system in cardiovascular physiology and pathophysiology is on the rise. This review focuses on the overall impact of dinucleoside polyphosphates in the purinergic system. Platelets, adrenal glands, endothelial cells, cardiomyocytes and tubular cells release dinucleoside polyphosphates. Plasma concentrations of dinucleoside polyphosphates are sufficient to cause direct vasoregulatory effects and to induce proliferative effects on vascular smooth muscle cells and mesangial cells. In addition, increased plasma concentrations of a dinucleoside polyphosphate were recently demonstrated in juvenile hypertensive patients. In conclusion, the current literature accentuates the strong physiological and pathophysiological impact of dinucleoside polyphosphates on the cardiovascular system.
Topics: Animals; Antihypertensive Agents; Cell Proliferation; Cystic Fibrosis; Dinucleoside Phosphates; Eye Diseases; Fibrinolytic Agents; Humans; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Protein Multimerization; Purinergic Agonists; Receptors, Purinergic; Respiratory Tract Diseases; Vasodilation
PubMed: 19563527
DOI: 10.1111/j.1476-5381.2009.00337.x -
Seminars in Dialysis 2009Dinucleoside polyphosphates constitute a group of endogenous vasoregulatory purines and pyrimidines with a strong impact on physiologic and pathophysiologic processes of... (Review)
Review
Dinucleoside polyphosphates constitute a group of endogenous vasoregulatory purines and pyrimidines with a strong impact on physiologic and pathophysiologic processes of the cardiovascular system. Recently, the importance of dinucleoside polyphosphates in chronic kidney disease (CKD) and uremia gained increasing interest. Although our knowledge about the impact of dinucleoside polyphosphates in CKD and uremia is just at the beginning, this article reviews the current knowledge of the physiologic and pathophysiologic role of dinucleoside polyphosphates in CKD and uremia.
Topics: Dinucleoside Phosphates; Humans; Uremia
PubMed: 19708989
DOI: 10.1111/j.1525-139X.2009.00588.x -
EXS 1993
Review
Topics: Animals; Base Sequence; Chromosome Mapping; DNA; DNA Modification Methylases; Dinucleoside Phosphates; Fragile X Syndrome; Genes; Humans; Methylation; Promoter Regions, Genetic; X Chromosome
PubMed: 8418949
DOI: 10.1007/978-3-0348-9118-9_8 -
Biochimica Et Biophysica Acta Dec 2011Mono and dinucleoside polyphosphates (p(n)Ns and Np(n)Ns) exist in living organisms and induce diverse biological effects through interaction with intracellular and... (Review)
Review
BACKGROUND
Mono and dinucleoside polyphosphates (p(n)Ns and Np(n)Ns) exist in living organisms and induce diverse biological effects through interaction with intracellular and cytoplasmic membrane proteins. The source of these compounds is associated with secondary activities of a diverse group of enzymes.
SCOPE OF REVIEW
Here we discuss the mechanisms that can promote their synthesis at a molecular level. Although all the enzymes described in this review are able to catalyse the in vitro synthesis of Np(n)Ns (and/or p(n)N), it is not clear which ones are responsible for their in vivo accumulation.
MAJOR CONCLUSIONS
Despite the large amount of knowledge already available, important questions remain to be answered and a more complete understanding of p(n)Ns and Np(n)Ns synthesis mechanisms is required. With the possible exception of (GTP:GTP guanylyltransferase of Artemia), all enzymes able to catalyse the synthesis of p(n)Ns and Np(n)Ns are unspecific and the factors that can promote their synthesis relative to the canonical enzyme activities are unclear.
GENERAL SIGNIFICANCE
The fact that p(n)Ns and Np(n)Ns syntheses are promiscuous activities of housekeeping enzymes does not reduce its physiological or pathological importance. Here we resume the current knowledge regarding their enzymatic synthesis and point the open questions on the field.
Topics: Dinucleoside Phosphates; Nucleotidyltransferases
PubMed: 21978831
DOI: 10.1016/j.bbagen.2011.09.010 -
Critical Reviews in Eukaryotic Gene... 2016Nucleotide-based second messengers transduce signals originating from both outside and inside the cell to adaptive responses accordingly. c-di-AMP is a newly established... (Review)
Review
Nucleotide-based second messengers transduce signals originating from both outside and inside the cell to adaptive responses accordingly. c-di-AMP is a newly established second messenger employed by many organisms. We summarize recent advances in bacterial c-di-AMP-mediated signaling, especially the interaction between c-di-AMP signaling and the host.
Topics: Bacteria; Dinucleoside Phosphates; Second Messenger Systems
PubMed: 27910745
DOI: 10.1615/CritRevEukaryotGeneExpr.2016016642 -
Progress in Retinal and Eye Research Nov 2007Diadenosine polyphosphates are a family of dinucleotides with emerging biochemical, physiological, pharmacological and therapeutic properties in the eye and other... (Review)
Review
Diadenosine polyphosphates are a family of dinucleotides with emerging biochemical, physiological, pharmacological and therapeutic properties in the eye and other tissues. These compounds are formed by two adenosine moieties linked by their ribose 5'-ends to a variable number of phosphates. Diadenosine polyphosphates are present as active components of ocular secretions such as tears and aqueous humour and they can activate P2 purinergic receptors present on the ocular surface, anterior segment and retina. Both metabotropic and ionotropic actions mediated by P2Y and P2X receptors, respectively are responsible for the control of processes such as induction of tear secretion, lysozyme production or acceleration of corneal wound healing. Inside the eye the dinucleotide Ap(4)A can reduce intraocular pressure by acting on P2Y(1) receptors present in trabecular meshwork cells and on P2X(2) receptors present on the cholinergic terminals located in the ciliary muscle. In the retina, derivatives of diadenosine polyphosphates can improve the re-absorption of fluids in retinal detachment. Altogether, diadenosine polyphosphates are not only dinucleotides with roles in the physiology of the eye but it is also possible that their properties may serve to help in the treatment of some ocular pathologies.
Topics: Animals; Dinucleoside Phosphates; Eye; Eye Diseases; Humans; Intraocular Pressure; Ocular Physiological Phenomena; Tears; Tissue Distribution; Wound Healing
PubMed: 17931952
DOI: 10.1016/j.preteyeres.2007.09.001 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Sep 2017Bacterial biofilm plays an important role in persistent microbial infection. Delineation of the formation and development of bacterial biofilm would provide a promising... (Review)
Review
Bacterial biofilm plays an important role in persistent microbial infection. Delineation of the formation and development of bacterial biofilm would provide a promising strategy to treat recalcitrant infection. c-di-AMP (Cyclic diadenosine monophosphate) is a recently identified second messenger of bacteria and involved in plethora of bacterial activities, including cell growth, cell wall homeostasis, biofilm formation and microbial pathogenicity. Here we review the recent literature pertinent to the role and molecular mechanisms of c-di-AMP in regulating biofilm formation of bacteria. The potential application of c-di-AMP and its related proteins in the development of novel antimicrobial therapeutics has also been discussed.
Topics: Bacteria; Biofilms; Dinucleoside Phosphates; Second Messenger Systems
PubMed: 28956388
DOI: 10.13345/j.cjb.170078 -
Journal of Autonomic Pharmacology Dec 19961. Diadenosine phosphates were isolated from platelets, adrenal gland and autonomic nerves. The presence of diadenosine phosphates in storage pools releasable into the... (Review)
Review
1. Diadenosine phosphates were isolated from platelets, adrenal gland and autonomic nerves. The presence of diadenosine phosphates in storage pools releasable into the circulation suggests an important role in the control of blood pressure, and potentially to a modulation of the actions of catecholamines. 2. Besides a role of the diadenosine phosphates in platelet aggregation, these agents have potent vasoactive properties. Vasoactive actions of the diadenosine phosphates were demonstrated in numerous vascular models including most of the physiologically important elements of blood pressure regulation. Mostly, the vasoactive action depends on the number of phosphates in the diadenosine phosphates. Vasodilation can be observed in intact vessels after administration of Ap2A, Ap3A and Ap4A whereas contraction is affected by Ap5A and Ap5A and Ap6A. Vasocontraction induced by the diadenosine phosphates in vascular smooth muscle cells is mediated by an increase in intracellular free Ca2+. 3. In vivo, intravenous injection of Ap4A lowers blood pressure whereas injections of Ap5A and Ap6A caused a prolonged increase in blood pressure. In blood, in contrast to ATP, diadenosine phosphates are relatively long-lived molecules, suggesting that the action of the latter is of intermediate time span. In a similar manner to the vasoconstrictor angiotensin II, diadenosine phosphates also act as mitogens. It can be assumed that diadenosine phosphates may be involved in pathophysiological events of circulation including hypertension and atherosclerosis.
Topics: Animals; Blood Pressure; Cattle; Dinucleoside Phosphates; Hemostasis; Humans; In Vitro Techniques; Muscle Tonus; Muscle, Smooth, Vascular; Neurotransmitter Agents
PubMed: 9131416
DOI: 10.1111/j.1474-8673.1996.tb00053.x