Latest Research on Adenosine Triphosphate: Jan 2021

Adenosine Triphosphate

Adenosine 5′-triphosphate (ATP) is a purine nucleotide found in every cell of the human body. In addition to its well established role in cellular metabolism, extracellular ATP and its breakdown product adenosine, exert pronounced effects in a variety of biological processes including neurotransmission, muscle contraction, cardiac function, platelet function, vasodilatation and liver glycogen metabolism. These effects are mediated by both P1 and P2 receptors. A cascade of ectonucleotidases plays a role in the effective regulation of these processes and may also have a protective function by keeping extracellular ATP and adenosine levels within physiological limits. In recent years several clinical applications of ATP and adenosine have been reported. In anaesthesia, low dose adenosine reduced neuropathic pain, hyperalgesia and ischaemic pain to a similar degree as morphine or ketamine. Postoperative opioid use was reduced. During surgery, ATP and adenosine have been used to induce hypotension. In patients with haemorrhagic shock, increased survival was observed after ATP treatment. In cardiology, ATP has been shown to be a well tolerated and effective pulmonary vasodilator in patients with pulmonary hypertension. Bolus injections of ATP and adenosine are useful in the diagnosis and treatment of paroxysmal supraventricular tachycardias. Adenosine also allowed highly accurate diagnosis of coronary artery disease. In pulmonology, nucleotides in combination with a sodium channel blocker improved mucociliary clearance from the airways to near normal in patients with cystic fibrosis. In oncology, there are indications that ATP may inhibit weight loss and tumour growth in patients with advanced lung cancer. There are also indications of potentiating effects of cytostatics and protective effects against radiation tissue damage. Further controlled clinical trials are warranted to determine the full beneficial potential of ATP, adenosine and uridine 5′-triphosphate. [1]

Extracellular adenosine triphosphate and adenosine in cancer

Adenosine triphosphate (ATP) is actively released in the extracellular environment in response to tissue damage and cellular stress. Through the activation of P2X and P2Y receptors, extracellular ATP enhances tissue repair, promotes the recruitment of immune phagocytes and dendritic cells, and acts as a co-activator of NLR family, pyrin domain-containing 3 (NLRP3) inflammasomes. The conversion of extracellular ATP to adenosine, in contrast, essentially through the enzymatic activity of the ecto-nucleotidases CD39 and CD73, acts as a negative-feedback mechanism to prevent excessive immune responses. Here we review the effects of extracellular ATP and adenosine on tumorigenesis. First, we summarize the functions of extracellular ATP and adenosine in the context of tumor immunity. Second, we present an overview of the immunosuppressive and pro-angiogenic effects of extracellular adenosine. Third, we present experimental evidence that extracellular ATP and adenosine receptors are expressed by tumor cells and enhance tumor growth. Finally, we discuss recent studies, including our own work, which suggest that therapeutic approaches that promote ATP-mediated activation of inflammasomes, or inhibit the accumulation of tumor-derived extracellular adenosine, may constitute effective new means to induce anticancer activity. [2]

A method for measuring adenosine triphosphate in soil

A method was devised for the extraction and measurement of adenosine 5′-triphosphate (ATP) in soil that minimizes sorption of ATP on the soil colloids. Soil was ultrasonified for 1 min with a solution containing trichloracetic acid (0.5 m). disodium hydrogen orthophosphate (0.25 m) and paraquat dichloride (0.1 m). The ATP content of the filtered extract was determined without further treatment in a scintillation spectrometer by the firefly luciferin-luciferase system. Recovery of added ATP was greater using the extratant containing trichloracetic acid, orthophosphate and paraquat than with trichloracetic acid alone or with a sulphuric acid extradant. Recoveries of added ATP ranged from 45% to 84% in thirteen different soils; ATP contents from 0.64 to 9.03 μg g−1 soil. [3]

One-time Exposure to General Anesthetics Alters Nociceptive Response and Nucleotide Hydrolysis in Infant Rats

Aims: The objective was to evaluate the single exposure of general anesthetics with or without a surgical procedure at postnatal day 14 (P14) on nociceptive behavioral responses. Furthermore, we evaluated ectonucleotidase activities at P14 and P30.

Place of Study: All experiments were performed at the Animal Experimentation Unit of Hospital de Clínicas de Porto Alegre. The Institutional Committee approved the experimental protocol f (GPPG-HCPA protocol No: 08149).

Methodology: Fourteen-day-old male Wistar rats were divided into two experimental designs (ED): the 1stED – control (C), isoflurane (ISO), isoflurane/surgery (ISO-SUR) and the 2nd ED – control (C), fentanyl/S(+)-ketamine (FK) and fentanyl/S(+)-ketamine/surgery (FK-SUR). Nociceptive responses were evaluated using the formalin and tail-flick tests, and the ectonucleotidase activities were evaluated by spinal cord synaptosome. All assessments were performed at P14 and P30.

Results: The FK and FK-SUR groups displayed an increased latency at P30. For the ectonucleotidase activity analysis, the following results were observed: (a) in the 1st ED, the ISO group displayed a reduction in ATPase and ADPase, and both ISO and ISO-SUR displayed a reduction in AMPase activity at P14; (b) in the 2nd ED, the FK group displayed an increase in AMPase activity at P14 and increased ATPase activity at P30, and both FK and FK-SUR exhibited an increase in AMPase activity at P30.

Conclusion: Our results indicate that single administration of general anesthetics at P14 is able to promote changes in the nociceptive response in the intermediate-term, and in the ectonucleotidase activities in the short- and medium-terms. [4]

Role of Interstitial Angiotensin II and ATP in Mediating Renal Injury Induced by Recurrent Insulin Induced Hypoglycemia

Aim: The present study hypothesizes that recurrent insulin induced hypoglycemia (RIIH) elevates renal interstitial ATP levels which in turn enhances AngII production. This interrupts the normal tubuloglomerular feedback (TGF) mechanism by stimulating afferent arteriolar vasoconstriction resulting in hypertension, which augments oxidative stress and could promote renal damage.

Study Design: In the present study we adopted a microdialysis technique, which is a minimally invasive tool for monitoring chronic changes in renal interstitial fluid.

Place and Duration of Study: Department of Basic Pharmaceutical Sciences, University of Louisiana at Monroe between September 2012 – October 2013.

Methodology: Eight male Sprague Dawley rats (200-225 g) were anesthetized and microdialysis probes were inserted into their renal cortex. Post-surgery rats were treated with insulin (7U/kg body weight) for 2 weeks. Food and water intake were monitored daily. Physiological saline was perfused through the probe and dialysate was collected daily after insulin dosing and analyzed for ATP by luciferin-luciferase assay and AngII by EIA. At the end of the experiment, the hearts and kidneys were collected and analyzed for oxidative stress by EPR (Electron Paramagnetic Resonance) spectroscopy using CMH and CPH spin probes.

Results: ATP and AngII levels were elevated from 31.65±4.4ng/µl (day 0) to 130.96±2.9 ng/µl (day 14) and 0.1±0.01 ng/ml (day 0) to 0.247±0.02 ng/ml(day 14), respectively. Elevation of peroxynitrite and superoxide anions were observed in the hearts and kidneys of insulin treated animals when compared to the control group.

Conclusion: Thus the present study utilizes real-time chronic collections of renal interstitial samples to identify a potential mechanism where iatrogenic hypoglycemia promotes hypertension via a synergistic relationship between interstitial ATP, AngII and developed oxidative stress. [5]

Reference

[1] Agteresch, H.J., Dagnelie, P.C., van den Berg, J.W.O. and Wilson, J.P., 1999. Adenosine triphosphate. Drugs, 58(2), pp.211-232.

[2] Stagg, J. and Smyth, M.J., 2010. Extracellular adenosine triphosphate and adenosine in cancer. Oncogene, 29(39), pp.5346-5358.

[3] Jenkinson, D. and Oades, J.M., 1979. A method for measuring adenosine triphosphate in soil. Soil Biology and Biochemistry, 11(2), pp.193-199.

[4] F. Medeiros, L., O. Battastini, A. M., Souza, A., R. Rozisky, J., Santos, V., Caumo, W. and Torres, I. (2014) “One-time Exposure to General Anesthetics Alters Nociceptive Response and Nucleotide Hydrolysis in Infant Rats”, Journal of Advances in Medicine and Medical Research, 4(22), pp. 3975-3989. doi: 10.9734/BJMMR/2014/6571.

[5] Prathipati, P., Alanazi, W., ., F., Jackson, D. W. and Jackson, K. E. (2015) “Role of Interstitial Angiotensin II and ATP in Mediating Renal Injury Induced by Recurrent Insulin Induced Hypoglycemia”, Annual Research & Review in Biology, 6(5), pp. 328-336. doi: 10.9734/ARRB/2015/16184.

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