Renal interstitial adenosine metabolism during ischemia in dogs

2001 ◽  
Vol 280 (2) ◽  
pp. F231-F238 ◽  
Author(s):  
Akira Nishiyama ◽  
Shoji Kimura ◽  
Hong He ◽  
Katsuyuki Miura ◽  
Matlubur Rahman ◽  
...  

The present study was conducted to determine the metabolism of renal interstitial adenosine under resting conditions and during ischemia. By using a microdialysis method with HPLC-fluorometric analysis, renal interstitial concentrations of adenosine, inosine, and hypoxanthine were assessed in pentobarbital-anesthetized dogs. Average basal renal interstitial concentrations of adenosine, inosine, and hypoxanthine were 0.18 ± 0.04, 0.31 ± 0.05, and 0.35 ± 0.05 μmol/l, respectively. Local inhibition of adenosine kinase with iodotubercidin (10 μmol/l in perfusate) or inhibition of adenosine deaminase with erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA; 100 μmol/l in perfusate) did not change adenosine concentrations in the nonischemic kidneys (0.18 ± 0.04 and 0.24 ± 0.05 μmol/l, respectively). On the other hand, treatment with iodotubercidin+EHNA significantly increased adenosine concentration (0.52 ± 0.07 μmol/l) with significant decreases in inosine and hypoxanthine levels (0.13 ± 0.03 and 0.19 ± 0.04 μmol/l, respectively). During 30 min of ischemia, adenosine, inosine, and hypoxanthine were significantly increased to 0.76 ± 0.29, 2.14 ± 0.45, and 21.8 ± 4.7 μmol/l, respectively. The treatment with iodotubercidin did not alter ischemia-induced increase in adenosine (0.84 ± 0.18 μmol/l); however, EHNA alone markedly enhanced adenosine accumulation (13.54 ± 2.16 μmol/l), the value of which was not augmented by an addition of iodotubercidin (15.80 ± 1.24 μmol/l). In contrast, ischemia-induced increases in inosine and hypoxanthine were inversely diminished by the treatment with iodotubercidin+EHNA (0.90 ± 0.20 and 9.86 ± 1.96 μmol/l, respectively). These results suggest that both adenosine kinase and adenosine deaminase contribute to the metabolism of renal interstitial adenosine under resting conditions, whereas adenosine produced during ischemia is mainly metabolized by adenosine deaminase and the rephosphorylation of adenosine by adenosine kinase is small.

1992 ◽  
Vol 263 (4) ◽  
pp. G487-G493 ◽  
Author(s):  
D. R. Sawmiller ◽  
C. C. Chou

The role of adenosine in postprandial jejunal hyperemia was investigated by determining the effect of placement of predigested food into the jejunal lumen on blood flow and oxygen consumption before and during intra-arterial infusion of dipyridamole (1.5 microM arterial concn) or adenosine deaminase (9 U/ml arterial concn) in anesthetized dogs. Neither drug significantly altered resting jejunal blood flow and oxygen consumption. Before dipyridamole or deaminase, food placement increased blood flow by 30-36%, 26-42%, and 21-46%, and oxygen consumption by 13-22%, 21-22%, and 26-29%, during 0- to 3-, 4- to 7-, and 8- to 11-min placement periods, respectively. Adenosine deaminase abolished the entire 11-min hyperemia, whereas dipyridamole significantly enhanced the initial 7-min hyperemia (45-49%). Both drugs abolished the initial 7-min food-induced increase in oxygen consumption. Dipyridamole attenuated (14%), whereas deaminase did not alter (28%), the increased oxygen consumption that occurred at 8-11 min. Adenosine deaminase also prevented the food-induced increase in venoarterial adenosine concentration difference. In separate series of experiments, luminal placement of food significantly increased jejunal lymphatic adenosine concentration and release. Also, reactive hyperemia was accompanied by an increase in venous adenosine concentration and release. This study provides further evidence to support the thesis that adenosine plays a role in postprandial and reactive hyperemia in the canine jejunum.


1986 ◽  
Vol 250 (4) ◽  
pp. H558-H566 ◽  
Author(s):  
F. L. Hanley ◽  
M. T. Grattan ◽  
M. B. Stevens ◽  
J. I. Hoffman

The role of cardiac interstitial adenosine as an important metabolite in coronary autoregulation has not been established. We therefore measured steady-state cardiac interstitial adenosine concentration at a high and a low coronary inflow pressure using an epicardial diffusion well in anesthetized dogs. Although coronary resistance for the high and low pressure points showed highly significant differences (P less than 0.001), adenosine averaged 302 +/- 98 and 286 +/- 91 (SD) pmol/ml for the high and low pressure points, respectively (P greater than 0.20). Cardiac interstitial adenosine concentration was then measured with and without an intracoronary infusion of adenosine deaminase catalytic subunit. Adenosine averaged 28 +/- 21 (SD) pmol/ml during the infusion compared with 281 +/- 68 during control conditions (P less than 0.001). Finally, pressure-flow relations were obtained with and without the adenosine deaminase infusion, and there was no loss of autoregulation in the pressure of adenosine deaminase. These findings indicate that intracoronary adenosine deaminase markedly reduces interstitial adenosine concentration, that cardiac interstitial adenosine concentration remains constant during autoregulation, and that the coronary bed autoregulates normally when interstitial adenosine is reduced to levels close to zero. We conclude that cardiac interstitial adenosine concentration is not an important component in coronary autoregulation.


1978 ◽  
Vol 174 (3) ◽  
pp. 965-977 ◽  
Author(s):  
J R S Arch ◽  
E A Newsholme

1. The maximal activities of 5′-nucleotidase, adenosine kinase and adenosine deaminase together with the Km values for their respective substrates were measured in muscle, nervous tissue and liver from a large range of animals to provide information on the mechanism of control of adenosine concentration in the tissues. 2. Detailed evidence that the methods used were optimal for the extraction and assay of these enzymes has been deposited as Supplementary Publication SUP 50088 (16pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K.,from whom copies can be obtained on the terms indicated in Biochem. J. (1978), 169, 5. This evidence includes the effects of pH and temperature on the activities of the enzymes. 3. In many tissues, the activities of 5′-nucleotidase were considerably higher than the sum of the activities of adenosine kinase and deaminase, which suggests that the activity of the nucleotidase must be markedly inhibited in vivo so that adenosine does not accumulate. In the tissues in which comparison is possible, the Km of the nucleotidase is higher than the AMP content of the tissue, and since some of the latter may be bound within the cell, the low concentration of substrate may, in part, be responsible for a low activity in vivo. 4. In most tissues and animals investigated, the values of the Km of adenosine kinase for adenosine are between one and two orders of magnitude lower than those for the deaminase. It is suggested that 5′-nucleotidase and adenosine kinase are simultaneously active so that a substrate cycle between AMP and adenosine is produced: the difference in Km values between kinase and deaminase indicates that, via the cycle, small changes in activity of kinase or nucleotidase produce large changes in adenosine concentration. 5. The activities of adenosine kinase or deaminase from vertebrate muscles are inversely correlated with the activities of phosphorylase in these muscles. Since the magnitude of the latter activities are indicative of the anaerobic nature of muscles, this negative correlation supports the hypothesis that an important role of adenosine is the regulation of blood flow in the aerobic muscles.


1992 ◽  
Vol 263 (2) ◽  
pp. H552-H558 ◽  
Author(s):  
T. Wang ◽  
R. M. Mentzer ◽  
D. G. Van Wylen

Dipyridamole is proposed to increase coronary blood flow (CBF) by inhibition of adenosine uptake into cells, resulting in an increase in interstitial fluid (ISF) adenosine and an adenosine-mediated vasodilation. The purpose of this study was to determine the changes in CBF and ISF adenosine, inosine, and hypoxanthine during dipyridamole infusion in the absence or presence of adenosine receptor blockade or adenosine deaminase. To sample cardiac ISF, cardiac microdialysis probes were implanted in the left ventricular myocardium of chloralose-urethan-anesthetized dogs and perfused with Krebs-Henseleit buffer. The metabolite concentration in the effluent dialysate was used as an index of intramyocardial ISF metabolite concentration. In response to dipyridamole, CBF and dialysate adenosine concentration increased 4.4-fold and 2.2-fold, respectively, whereas dialysate inosine was unchanged and dialysate hypoxanthine decreased 50%. Adenosine receptor blockade, achieved by intracoronary 8-(p-sulfophenyl)theophylline infusion, attenuated the increase in CBF induced by dipyridamole without changing dialysate adenosine concentration. Adenosine deaminase fully attenuated the dipyridamole-induced increases in CBF and dialysate adenosine. These results demonstrate that dipyridamole increases ISF adenosine in the dog and suggest that adenosine is the sole mediator of dipyridamole-induced coronary vasodilation.


2021 ◽  
Author(s):  
Anuja N Mulmule ◽  
Arti R Mishra ◽  
Vinita R Hutke ◽  
Seema D Shekhawat ◽  
Amit R Nayak ◽  
...  

Adenosine Deaminase (ADA) estimation in all forms of tuberculosis (TB) is done by several investigators, however, there has been a lot of debate about the use of the ADA for TB diagnosis. In the present study, to overcome this debate, we have planned a large scale study in the Central India population for all forms of TB i.e. pulmonary TB (PTB), tuberculous meningitis (TBM), TB arthritis (TBAR), and abdominal tuberculosis (ATB) to access the performance of ADA for diagnosis of TB. In addition to that, we have also studied the performance of the ADA test in the prognosis of TB. ADA activity was evaluated using the method of Guisti and Galanti. To evaluate the role of the ADA test as a prognostic marker in TB, we have collected follow-up clinical samples of PTB and TBM cases. The sensitivity of the ADA test is impressive in all forms of TB clinical samples analyzed for the study (PTB [82%], TBM [85%] TBAR [85%]), and (ATB) [84%]. However, the specificity was variable as ADA test results were found to be satisfactory for extrapulmonary TB (EPTB) cases ( i.e TBM [89%], (ATB) [88%], TBAR [88%]), on the other hand, poor specificity was observed in PTB cases (PTB [48%]). In the follow-up clinical samples (collected before and after anti-TB treatment [ATT]). In the follow-up samples, the result of the ADA test was observed to have declined drastically thereby showing a negative value after the ATT. Our study, which consists of a large number of samples, suggests that the ADA has very limited value in the diagnosis of PTB, and hence it is not recommended for PTB diagnosis. On the other hand, the ADA test is found to be useful for the diagnosis of EPTB in correlation to the patient's clinical condition. Along with the above-mentioned aspects and according to our follow-up study results, we recommend that ADA be useful as a prognostic indicator for TB.


1993 ◽  
Vol 13 (2) ◽  
pp. 201-207 ◽  
Author(s):  
Veronica M. Sciotti ◽  
David G. L. Van Wylen

The purpose of this study was to determine the changes in interstitial fluid (ISF) adenosine and cerebral blood flow (CBF) during inhibition of adenosine kinase or adenosine deaminase. Brain microdialysis was used to (a) measure CBF (H2 clearance), (b) sample cerebral ISF, and (c) deliver drugs locally to the brain. Microdialysis probes were implanted bilaterally in the caudate nucleus of halothane-anesthetized rats ( n = 11). One probe was perfused with artificial cerebrospinal fluid (CSF) containing iodotubercidin (IODO), an adenosine kinase inhibitor, while the other probe was perfused with erythro-2-(2-hydroxy-3-nonyl)adenine (EHNA), an adenosine deaminase inhibitor. Both probes were subsequently perfused with EHNA + IODO. Finally, 8-( p-sulfophenyl)theophylline (SPT), an adenosine receptor antagonist, was added to EHNA + IODO in one probe, while the other probe continued to receive only EHNA + IODO. CBF and dialysate adenosine levels increased with either EHNA or IODO; however, the increases were greater with IODO. EHNA + IODO further increased CBF and dialysate adenosine. The hyperemia observed with EHNA + IODO was abolished by adenosine receptor blockade. These data suggest that basal adenosine levels are influenced to a greater extent by adenosine kinase than by adenosine deaminase. In addition, the increased CBF observed with inhibition of adenosine metabolism and the attenuation of this vasodilatory response with adenosine receptor blockade support a role for adenosine in CBF regulation.


1999 ◽  
Vol 173 ◽  
pp. 249-254
Author(s):  
A.M. Silva ◽  
R.D. Miró

AbstractWe have developed a model for theH2OandOHevolution in a comet outburst, assuming that together with the gas, a distribution of icy grains is ejected. With an initial mass of icy grains of 108kg released, theH2OandOHproductions are increased up to a factor two, and the growth curves change drastically in the first two days. The model is applied to eruptions detected in theOHradio monitorings and fits well with the slow variations in the flux. On the other hand, several events of short duration appear, consisting of a sudden rise ofOHflux, followed by a sudden decay on the second day. These apparent short bursts are frequently found as precursors of a more durable eruption. We suggest that both of them are part of a unique eruption, and that the sudden decay is due to collisions that de-excite theOHmaser, when it reaches the Cometopause region located at 1.35 × 105kmfrom the nucleus.


Author(s):  
A. V. Crewe

We have become accustomed to differentiating between the scanning microscope and the conventional transmission microscope according to the resolving power which the two instruments offer. The conventional microscope is capable of a point resolution of a few angstroms and line resolutions of periodic objects of about 1Å. On the other hand, the scanning microscope, in its normal form, is not ordinarily capable of a point resolution better than 100Å. Upon examining reasons for the 100Å limitation, it becomes clear that this is based more on tradition than reason, and in particular, it is a condition imposed upon the microscope by adherence to thermal sources of electrons.


Author(s):  
K.H. Westmacott

Life beyond 1MeV – like life after 40 – is not too different unless one takes advantage of past experience and is receptive to new opportunities. At first glance, the returns on performing electron microscopy at voltages greater than 1MeV diminish rather rapidly as the curves which describe the well-known advantages of HVEM often tend towards saturation. However, in a country with a significant HVEM capability, a good case can be made for investing in instruments with a range of maximum accelerating voltages. In this regard, the 1.5MeV KRATOS HVEM being installed in Berkeley will complement the other 650KeV, 1MeV, and 1.2MeV instruments currently operating in the U.S. One other consideration suggests that 1.5MeV is an optimum voltage machine – Its additional advantages may be purchased for not much more than a 1MeV instrument. On the other hand, the 3MeV HVEM's which seem to be operated at 2MeV maximum, are much more expensive.


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